PolySciTech Technical Blog

Light weight in-vivo imaging system "ELVIS"

2012-01-26T19:29:00.000-05:00

Polyscitech is proud to present our first research grade In-Vivo imaging system. Unlike other systems which weight more than a hundred pounds and costs tens of thousands of dollars the ELVIS system can be easily set-up and taken down and put away in a backpack with a price substantially less than traditional In-Vivo imaging systems. This system as it is allows for detection of near IR fluorescence but other modes will soon be available including FITC (ex488/em525).

The image shows a mouse injected subcutaneously with NIR fluorescent microparticles imaged both in bright-mode (normal vision) and in Near-IR.

Polyvivo folate intermediates

2012-01-26T09:11:00.003-05:00

The folate conjugated PEG's are commonly used for targeted delivery to cancer cells. The following links to full-text articles describe this usage.

http://www.dds.re.kr/pds/files/essay/4.pdf

http://clincancerres.aacrjournals.org/content/6/5/1949.full

http://www8.utsouthwestern.edu/utsw/facdir/cma/fileuploads/8/facdir76088/FunctionalizedMicellesForCancer.pdf

The Polyvivo intermediates contain a folate conjugated to a PEG with the alternate end left with a functional group (e.g. COOH or alcohol) which can be chemically attached to some other molecule such as the drug, etc.

PolyVivo AK30 PEG-PLGA water solubility

2012-01-20T12:51:00.001-05:00

Recent product PolyVivo AK30 (mPEG-PLGA 5000-4000Da) is water soluble to form a cloudy solution with 1% w/v. Upon shaking a gentle foam is easily formed (see picture) indicating surfactant behavior of this material. This product is a good research compliment to our current water soluble product AK09 (mPEG-P(DL)La 2000-2200) due to their varying block lengths and compositions.

Select PolyVivo polymers on sale

2012-01-13T16:45:00.002-05:00

The Polyvivo product line includes biodegradablehydrophilic block copolymers. These polymers are block copolymers ofhydrophillic, biocompatible poly(ethylene glycol) (PEG), and biodegradablepolymers such as poly(lactide-co-glycolide) (PLGA), poly(caprolactone) (PCL),and poly(lactide) (PLA). Ideal for delivery of poorly soluble drugs such aspaclitaxel. PolyVivo polymers can be used for a wide variety of drug deliveryplatforms, including polymer micelles, thermoreversable hydrogels and otherformulations. Select polymers are now atan additional 25% discount. See (http://www.polyscitech.com/) for more.

New Yard-Sale items available

2012-01-13T11:27:00.003-05:00

Several new-to-you items are available on the Yardsale site (http://polyscitech.com/YardSale/): These include a Syringe Pump (KDS410), Microscope video camera (Cole-Parmer 49901-20), nalgene pipette washer, and a Refractometer (Baush and Lomb Model 334610). All of these are being sold at extremely low prices and could be a perfect compliment to your laboratory equipment.

Flamma Fluor Labelled Polyvivo polymers

2012-01-11T15:49:00.002-05:00

Flamma Fluor dyes conjugated to Polyethylene glycol and Polyesters are now available. These materials combine the bioresorbable nature of polyvivo polymers with the brightly fluorescent Flamma tracking dyes to allow for in-vivo imaging and other fluorescent techniques

Diamine endcapped PLGA now available

2012-01-11T13:03:00.004-05:00

Di-amine encapped PLGA reactive intermediate (catalogue #AI21) is now available. This allows for custom functionalization of the polymer at both ends for fluorescent staining or other uses.

Thermogelling Polyvivo AK12 publication

2011-12-07T14:34:00.001-05:00

The use of thermogelling PLGA-PEG-PLGA (PolyVivo AK12) (an alternate to former Macromed's Regel) for delivery of microparticles has recently been published by Stanford University for its use as a thermogelling agent.

Drug Release from Electric-Field-Responsive Nanoparticles Jun Ge, Evgenios Neofytou, Thomas J. Cahill III, Ramin E. Beygui, and Richard N. Zare ACS NanoArticle ASAP

Abstract:
"We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control."

Image from publication referenced above

PolyVivo PLCL

2011-12-06T10:34:00.001-05:00

PolyVivo Product AK-PLCL-75K has highly strong and elastic properties as shown in this video. Most biodegradable polymers are highly brittle and shatter if compressed. However, an unplasticized clump of this material easily handles being compressed by a 1/4 inch steel ball due to its elastic nature.

AK-PLLA-FL

2011-11-23T16:57:00.001-05:00

Now you see it now you don't. Images show 1mg/ml AK-PLLA-FL in DCM used to write the name "AK-PLLA-FL" on a piece of paper both in room lighting and under fluorophone settings.

2011-11-22T17:11:00.001-05:00

Image shows 1mg/ml AK-PLLA-40-FL dissolved in dichloromethane imaged using a droid smart phone and our soon to be available Fluorophone imaging kit which allows for anyone with a smart phone and a desk lamp to do fluorescent imaging.

Drug delivery patent using PST technology

2011-11-21T15:43:00.001-05:00

A former name referring to PEG-polyester type polymers from Akina was "Polycelle". This is referenced in a patent:
Method for Prevention or Treatment of Inflammatory Disease
Application number: 11/572,797
Publication number: US 2008/0113016 A1
Filing date: Jul 25, 2005
Inventors: Gary Steven Firestein, David Louis Boyle, Linda Sue Sorkin
"Methods are provided for prevention or treatment of inflammatory disease in a mammal by administering an inhibitor of mitogen activated (MAP) kinase system to the mammal in a therapeutic amount to the mammal in need thereof. The MAP kinase inhibitor is targeted to the central nervous system of the mammal. Methods are further provided for prevention or treatment of inflammatory disease in a mammal by administering an antagonist of TNF-α to the mammal in a therapeutic amount to the mammal in need thereof. The TNF-α antagonist is targeted to the central nervous system of the mammal."

PolyVivo Patents and former name

2011-11-21T09:37:00.001-05:00

One former name of "Polyvivo" products is "PolyShield". There are some patents which make reference to this prior name. Generally speaking the original designation "PolyShield" only included what is today Polyvivo AK01-08.

“Shape-Changing Medical Device, Kit, Method OfProduction, And Method Of Use”

Inventors: Stevan Nielsen, Bodo Quint, GerdSeibold, Ib Erling Joergensen

Application number: 12/738,623
Publication number: US 2010/0305603 A1
Filing date: Oct 17, 2007
"The present disclosure relates to treatment of disorders in the heart rhythm regulation system and, more particularly, to a medical device for tissue cutting and/or migrating wherein the cutting and/or migrating is at least partly actuated by the swelling of a swellable material. The disclosure furthermore relates to a method of producing such a medical device, a kit of such medical devices, and a method for treating such disorders."

This patent references using PolyShield (Polyvivo) polymers.

Patents using Akina materials

2011-11-21T09:31:00.001-05:00

There are several patents which mention the usage of PolySciTech polymers or other materials.

"Materials and Methods for Preparation of alkaline earth ferrates from alkaline earth oxides, peroxides and Nitrates"
Inventors: John Alfred Thompson, John Hen

Application number: 12/627,900
Publication number: US 2010/0151049 A1
Filing date: Nov 30, 2009

"The subject invention concerns methods for preparing alkaline earth ferrates and the preparation of hemostatic compositions from alkaline earth ferrates. In one embodiment, the alkaline earth ferrate is strontium ferrate. In one embodiment, methods of the invention comprise heat treating mixtures of alkaline earth oxides and/or peroxides with iron oxides, such as hematite or magnetite. The subject invention also concerns hemostatic compositions produced using metallic oxides that are reacted with alkaline earth oxides and/or peroxides and the methods used to produce the hemostatic compositions."

Mentions aquagel superporous hydrogel from Akina, Inc.

Patents Using PolySciTech materials

2011-11-21T09:25:00.001-05:00

There are several patents which mention the usage of PolySciTech polymers or other materials.

"Vessel Protective Device"
Inventors: Ann Prewett, Mark Dingledine, Alan C. Chen
Application number: 12/573,670
Publication number: US 2010/0222881 A1
Filing date: Oct 5, 2009
"The present disclosure relates to a vessel/tissue protection device having a polymer coated reinforcing layer. The polymer can comprise a biocompatible polymer that will not promote tissue in-growth or attachment, such as segmented polyurethane, polycarbonate urethane, polyether urethane, polyacrylonitrile, etc. The reinforcing layer can comprise any suitable woven, non-woven, knitted, or braided reinforcing polymer, fabric, or foil that is biocompatible and capable of holding a suture, staple, or other attachment device."

Materials listed include polyaspartic acid and a variety of polyesters sourced from Akina, Inc.

PLCL (50:50, 75kDa) now available

2011-11-17T17:06:00.001-05:00

New polyvivo product available is 50:50 Poly(L-lactide-co-caprolactone) with a MW ~75,000Da. This biodegradable polymer has high elasticity and mechanical strength for applications where mechanical properties are key.

AK-PLLA-40K-Fl visibility

2011-11-11T12:07:00.001-05:00

Triangular shaped cast film made by casting and drying at room temperature 1mg/ml AK-PLLA-40K-FL/DCM imaged at 4X magnification under Olympus BX51 microscope with DP70 camera using FITC mode and 1 second of exposure time (ambient lighting conditions). The green fluorescent cast film is easily vissualized.

2011-11-10T17:10:00.001-05:00

Just some of the Polyscitech team from left to right: Steven Gates, Jennifer Berman, Faye Jessmon, and John Garner. You can see more at PolySciTech's facebook page.

Website catalogue

2011-11-03T12:44:00.000-04:00

To make our polymers easier to find there is now an interactive version of our catalogue available at (http://www.polyscitech.com/products/polyvivo/Table-PEG-PLA-PLGA-PCL-copolymers-and-linear-water-soluble-fluorescent-intermediate-polymers.php) just use the buttons at the top to narrow down the catalogue to exactly the polymer type you are looking for.

NHS activated flamma fluor dyes available

2011-11-01T11:43:00.005-04:00

New flamma fluor dyes with reactive N-hydroxysuccinimide moieties are now available. N-hydroxysuccinimide is highly reactive towards amines which allows for rapid and efficient labelling of proteins, peptides, amine endcapped polymers, and other amine bearing molecules. The dyes currently available are FNR-552, FNR-648, and FNR-749. You can see these and others at http://www.polyscitech.com/products/flammafluor/catalogue.php

PLGA-Glucose

2011-10-27T14:49:00.002-04:00

New product available is PLGA-Glucose star shaped biodegradable polymer. two products available now are the original (~30kDa MW) and the 50Kda version. Both of these can be found at our catalogue (http://www.polyscitech.com/products/polyvivo/catalogue.php)

Funakoshi Distributorship

2011-10-04T17:08:00.002-04:00

PolySciTech products are distributed in Japan via our partners in Funakoshi. They have recently published an advertisement for our products. For purchasing in Japan please go to http://www.funakoshi.co.jp/

BMES meeting Hartford, CT Oct 12-15

2011-10-04T14:06:00.004-04:00

PolySciTech division will be at the BMES meeting in Hartford, CT this October 12-15th presenting at Booth #723. BMES meeting details available at http://www.bmes.org/aws/BMES/pt/sp/home_page

Polyvivo AK09 reverse protein emulsion

2011-09-30T15:55:00.003-04:00

As a test for reverse emulsification (e.g. water/oil) 10% w/v Polyvivo AK09 (mPEG-PDLLA) was dissolved in dichloromethane. FITC labelled bovine serum albumin was dissolved in phosphate buffer (pH~7) at 2.5mg/ml. The AK09 solution (~5ml) was stirred at 2000RPM using a spiral stirrer and IKA lab-egg stir-driver. To the stirring solution 100 ul of the BSA-FITC solution was added and allowed to stir for 1 minute prior to stirrer removal. The same process was done using a blank dichloromethane control. The results macroscopically are shown in the picture above. Without AK09, BSA-FITC (yellow due to FITC) is seperated from the DCM layer with AK09 however more of a homogenous mixture is maintained. The 10% polyvivo AK09 solution was imaged under 10X fluorescence and fluorescent BSA-FITC was observed to be randomly distributed throughout the DCM (image below).

Yard Sale

2011-09-30T09:17:00.001-04:00

Since there is only so much lab space and we are over-stocked on some equipment PolySciTech is having an online yard sale. Check out some of the equipment available for purchase in many cases for half the price of new at http://polyscitech.com/YardSale/. Contact me to learn more about each piece as well as for purchasing.

PLCL-PEG-PLCL AK28 now available

2011-09-20T13:44:00.001-04:00

Now there is a triblock Poly(lactic-co-caprolactone)-Poly(ethylene glycol)-Poly(lactic-co-caprolactone) (~5700-4600-5700Da) available for purchase (Catalogue Polyvivo AK28). This material combines desirable mechanical and thermal properties for moderate temperature processing. See more at: http://www.polyscitech.com/products/polyvivo/catalogue.php#BlockCopolymers

Flamma Fluor Publication

2011-09-02T13:55:00.000-04:00

The Use of Flamma Fluor for in-vivo imaging hase been published:

"Hybrid Nanocrystals: Achieving Concurrent Therapeutic and Bioimaging Functionalities toward Solid Tumors" Rongsheng Zhao, Christin Hollis, Hua Zhang, Lili Sun, Richard Gemeinhart, Tonlei Li. Molecular Pharmaceutics Article ASAP.

http://tigger.uic.edu/labs/bpslab/PDF/MolPharmaceutics_8_x_2011.pdf

Polymer-amine (AI05-10) plus flamma fluor usage

2011-07-14T13:23:00.003-04:00

Amine endcapped Polyesters are widely applicable for an array of modifications. Materials with a vinyl sulfone or N-hydroxysuccinimide functional unit are highly reactive towards these polyesters allowing for custom endcaps to be placed on the polyester. In the above picture Poly(L-lactic acid) amine endcap (Polyvivo intermediate AI08) was reacted with Flamma Fluor FPI-749 in dichloromethane at room temperature overnight, subsequently purified and then converted into microparticles via a typical homogenization technique (~5-10% polymer in DCM pipetted into 0.5% PVA Mowiol 4-88 with homogenization at 10,000RPMs) and the resultant microparticles are shown in the picture above under brightfield imaging. In this imaging mode the near-IR flourescent dye lends a teal-colored apearance to the microparticles. Under near-IR in-vivo imaging modes this dye has proven itself useful for tracking materials in the skin. Both Flamma Fluor FPI-749 and reactive intermediates can be purchased from the PolySciTech division of Akina, Inc.

Moderate temperature melt processing

2011-06-22T21:32:00.006-04:00

Dear (Customer),

I did a very brief experient on AK15 to check for its melting properties. I tossed 3 little pieces in scint vials and purged in some argon then put each one on a hotplate set to either 40,60, or 80C respectively. After half an hour the 60 and 80C had melted to stick to the bottom of the scint vial whereas the 40C one did not so it's reasonable to state the melting transition on this one is between 40-60C. The picture here is the vials laying on their side after heating and the 40C piece fell off the bottom but the other two are adhered. At room temperature this material is solid amorphous yet it can be melt processed at relatively moderate temperatures.

Example microparticle formulation

2011-06-17T16:04:00.003-04:00

The image shown here is a set of flourecently labeled microparticles made by dissolving a 1:1 mixture at 5% w/v of polyvivo AK-PLLA-25 and AK-PLGA-FL-1. The microparticles were made by traditional emulsion technique. This solution was pipetted into an emulsion of 0.5% PVA (mowiol 4-88) with an emulsion maintained by homogenization at ~10,000RPM for 2 minutes followed by centrifugation to collect and redisperse. Images were taken on a traditional fluorescent microscope (Olympus BX51) under FITC mode and is shown here. Due to the flourescein endcap on the AK-PLGA-FL-1 these microparticles are rendered flourescent which makes them sensitive to microscopy techniques allowing them to be tracked during experiments.

Both AK-PLGA-FL-1 and AK-PLLA-25 are available for sale on the polyvivo catalogue http://www.polyscitech.com/products/polyvivo/catalogue.php

PolyVivo Emulsions

2011-05-18T12:17:00.002-04:00

Dear (CUSTOMER),

I performed a brief experiement on one of these which may be helpful to you. I dissolved AK09 (B#1) as 1% w/v in 50 ml water and emulsified with a homogenizer (IKA T25 Basic) with homogenization ~9000RPM I added 100ul of 10% PLGA (Resomer RG503H Boeinger Ingelheim) plus ~0.1% nile red dye (fluorescent tracer) dissolved in dichloromethane. I let this continue to homogenize for about 1 minute then pulled out. The 1% AK09 solution vissually forms bubbles (like soap water) and I pipetted a small amount of the solution out onto a microscope slide and imaged using a BX51(Olympus) microscope under TRITC fluorescence mode and obtained the attached picture. As you can see emulsion microparticles (little red droplets, in this case ~10-20um in size) can be obtained using AK09 via this method.

As for making microparticles there is going to be a wide range of sizes you can make based on homogenization speed (rule of thumb, faster is smaller but there is such thing as too fast), surfactant concentration, surfactant type (diblock and triblock copolymers will have different micelle sizes and these sizes will also depend on surfactant concentration), polymer solvent type (solvents interact differently with water and some prefer evaporation versus extraction). Inevitably with all emulsion type there will be a bit of loss as some polymer will ppt out to rapidly/slowly and not be microparticles but this method will generally yield a fair amount of microparticles. I encourage you to check out a paper where they make a couple of different PLGA microparticle sizes. Here they use traditional non-degradable surfactants but the concepts are still similar. (H. Jeffery, S.S. Davis, D.T. O'Hagan, The preparation and characterisation of poly(lactide-co-glycolide) microparticles. I: Oil-in-water emulsion solvent evaporation, International Journal of Pharmaceutics, Volume 77, Issues 2-3, 15 November 1991, Pages 169-175.) The primary advantage here is typically whatever surfactant you use will inevitibally end up adherent to the external part of your microparticle as it forms inside the micelle so with polyvivo surfactants you would theoretically end up with microparticles covered with with polyvivo polymer.

I would suggest preparing and using polyvivo surfactant solution pretty much immediately as you need it. If you can't use it soon store in a refrigerator but after a few days in water the properties may change some as the polyvivo degrades.

PolyVivo AK02 Solubility

2011-04-22T08:54:00.002-04:00

There have been a few questions regarding the solubility of diblock copolymer mPEG-PLGA (2000-4000) PolyVivo AK02. This polymer exhibits partial solubility in most organic solvents (THF, Acetone, DMSO) but leaves a small amount of crystalline material. The ideal organic solvent for this material is dichloromethane in which it is completely soluble.

CRS Meeting

2011-04-07T12:50:00.003-04:00

John Garner will be at the controlled Research Society Meeting this year in National Harbor, Maryland, July 30 – August 3, 2011. Feel free to drop by and say "hi". Click below to learn more about this meeting. http://www.controlledreleasesociety.org/meeting/default.cfm

PolyVivo AK24 thermosensitive

2011-03-31T14:16:00.002-04:00

Akina has a new thermosensitive PolyVivo product in addition to the current AK12. PolyVivo AK24 has a higher gelation point (35-40C) than AK12 and exhibits strong viscosity in the body temperature range. You can see a movie of this polymer flowing at both 4C and 37C at (http://www.youtube.com/watch?v=wB4KQXOvaoo) as well as see rheometry data for 20% solution at (http://www.akinainc.com/pdf/AK24-AK23%20Thermosolution%20properties.pdf) this and other PolyVivo polymers are available at our website (http://www.polyscitech.com/products/polyvivo/)

PolyVivo AK23

2011-03-31T14:13:00.003-04:00

A new product is available PolyVivo AK23. This is a water-soluble short chain PEG-PLGA diblock copolymer which works well for emulsion/solubility improvement applications. See the COA at (http://www.akinainc.com/pdf/COA-No-23-B0.pdf) this and other PolyVivo polymers can be seen at our homepage (http://www.polyscitech.com/products/polyvivo/)

PolyVivo AK12 In-Vivo Surgical Usage

2011-03-31T09:12:00.003-04:00

The note below is from an answer to a question from a customer who was planning to use AK12 for in-vivo animal work. The customer's identity and any proprietary details regarding their work have been removed. Generally this is the same advice that would be given for in-vivo usage with this polymer as a thermogel.:

Dear (Customer),

Thanks for asking about this. For creating a good thermosensitive gel using AK12 the best method is to dissolve as a solution between 10-30% (w/v) in water or saline and then add your [...omitted...] to the solution (testing at Akina has shown that it doesn't really matter too much what else is in the aqueos solution, checkout: http://www.akinainc.com/pdf/AK12%20Viscosity%20and%20Thermal%20properties.pdf). Most of our work has focused around 20% w/v and this is known to solidify nicely but still be easily dissolved at cold temperatures so this would be a suggested concentration to work with. So a couple of important notes:

1. AK12 due to being a short polymer is extremely sticky and viscous in its dry and natural state. I can't really change that fact (even though I wish I could), that's simply the physical form that polymers of this type/size take. If you want to subdivide/move to a new container I would suggest avoiding using a spatula as it will stick strongly to anything it touches. A better idea is to make up the aqueos solution in the bottle the AK12 came in (e.g. adding 5ml of saline to ~1g AK12 would yield a 20% soln) and then transfer/subdivide the solution of known concentration.

2. AK12 only dissolves cold. This is somewhat similar to pluronic in that (counter-intuitively) the best way to dissolve AK12 is to put it in a refrigerator (whatever you do, do not heat to dissolve! This will only damage the polymer and make it dissolve even slower). The dissolution also takes some time (at the very least overnight) so best to let it dissolve overnight or even better a few days and then use it. Keep this in mind when planning timing for your animal surgeries, you will need to dissolve the AK12 well in advance of your surgery date. At 4C the AK12 solution is stable for about 2-3 weeks. After a month or so in aqueous solution in the fridge it will gelate due to degradation and not work as a cold-water soluble material so if you find some "left-overs" much later on chances are they may not be good.

3. Make sure to keep the AK12 solution cold right up to the time of surgery. May even be worth your while to take a small styrofoam box in with you to surgery with the AK12 solution in it and a small ice-pack. AK12 is a little "trigger-happy" when it comes to gelling and will start to solidify up even if you are working in a warm room (27-30C) so for injection/insertion purpose keeping it cold is optimal.

Hope this helps and good luck,

John Garner Manager Akina, Inc. 1291 Cumberland Avenue West Lafayette, IN 47906 Phone: 765-464-0501 ext6# Fax: 765-464-0820 jg@akinainc.com jgakinainc@gmail.com http://www.akinainc.com/

FTIR spectra available

2011-03-02T12:42:00.002-05:00

FTIR spectra are now available for most polyvivo products. They are in the product information category at http://www.polyscitech.com/products/polyvivo/

Thermogelation White Papers

2011-02-26T21:01:00.002-05:00

Technical papers relating to thermogelation experiments performed at Akina are available online.

AK12 gelation properties
http://www.akinainc.com/pdf/AK12%20Viscosity%20and%20Thermal%20properties.pdf

AK19 gelation properties
http://www.akinainc.com/pdf/AK19%20Batch%20Number%201%20Gelation%20tests.pdf

Thermogelation Additives

2011-02-03T16:06:00.002-05:00

The thermogelation properties of low molecular weight triblock copolymers (like PolyVivo AK12 and AK19) can be fine-tuned using either PEG1000 to slightly lower the gelation temperature or NaSCN to raise the gelation temperature. PolyVivo polymers can be purchased at http://www.polyscitech.com/products/polyvivo/

The tuning process is described more thoroughly in the following research paper:

Myung Seob Shim, Hyung Tak Lee, Woo Sun Shim, Insun Park, Hyunjung Lee, Taihyun Chang,Sung Wan Kim, Doo Sung Lee “Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water” J Biomed Mater Res 61: 188–196, 2002

Link To Full-text
http://www.postech.ac.kr/chem/poly/pdf/112.pdf

PLA-PEG microparticle drug delivery

2010-12-21T14:32:00.000-05:00

The below article discusses the usage of PLA-PEG for nanoparticle drug delivery. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"Drug-loaded biodegradable PLA, PLA/PEG microspheres were prepared by the coacervation technique, by solvent evaporation and by the emulsion method. The effects of drug properties, particle size, drug loading and method of microencapsulation on the in vitro drug dissolution were also examined. According to the results, PLA/PEG copolymer was more hydrophilic than PLA homopolymer, and with lower glass transition temperature. PLA/PEG microparticulates were not as smooth as that of PLA. Drug release from microspheres was effected by the properties of PLA/PEG copolymers. The release rate of the hydrophobic drug, lidocaine, encapsulated in the polymer PLA/PEG copolymer, was faster than that in a pure PLA homopolymer. The same results also held for the hydrophilic drug, propranolol hydrochloride. Microspheres obtained by the emulsion method were porous and with adequate drug permeability"

Y.-Y. Huang, T.-W. Chung, T.-w. Tzeng, Drug release from PLA/PEG microparticulates. International Journal of Pharmaceutics 156(1) (1997) 9-15.

Full text: http://ntur.lib.ntu.edu.tw/bitstream/246246/127957/1/07.pdf

PLA-PEG nanoparticles for drug delivery

2010-12-21T14:28:00.002-05:00

The article discusses the usage of PLA-PEG for nanoparticle drug delivery. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract in image.

M. Tobío, R. Gref, A. Sánchez, R. Langer, M.J. Alonso, Stealth PLA-PEG Nanoparticles as Protein Carriers for Nasal Administration. Pharmaceutical Research 15(2) (1998) 270-275. http://www.springerlink.com/content/r3u8475667142u24/

PLA-PEG electrospun gene delivery

2010-12-21T14:26:00.000-05:00

The below article discusses the usage of PLA-PEG for electrospinning a scaffold for gene delivery. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"The present work utilizes electrospinning to fabricate synthetic polymer/DNA composite scaffolds for therapeutic application in gene delivery for tissue engineering. The scaffolds are non-woven, nano-fibered, membranous structures composed predominantly of poly(lactide-co-glycolide) (PLGA) random copolymer and a poly(D,L-lactide)-poly(ethylene glycol) (PLA-PEG) block copolymer. Release of plasmid DNA from the scaffolds was sustained over a 20-day study period, with maximum release occurring at ~2 h. Cumulative release profiles indicated amounts released were approximately 68-80% of the initially loaded DNA. Variations in the PLGA to PLA-PEG block copolymer ratio vastly affected the overall structural morphology, as well as both the rate and efficiency of DNA release. Results indicated that DNA released directly from these electrospun scaffolds was indeed intact, capable of cellular transfection, and successfully encoded the protein [beta]-galactosidase. When tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli of ~35 MPa, with ~45% strain initially. These values approximate those of skin and cartilage. Taken together, this work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning"

Y.K. Luu, K. Kim, B.S. Hsiao, B. Chu, M. Hadjiargyrou, Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. Journal of Controlled Release 89(2) (2003) 341-353. (http://www.sciencedirect.com/science/article/B6T3D-48CT09D-M/2/c5cb0024a0c3c9a6cbe2acc1452ebac2)

Expanded straight chain catalogue

2010-12-06T17:03:00.002-05:00

Akina now has an extended catalogue of straight chain and non-block biodegradable polymers in the "other" category. These include PLGA-(75:25) and Poly-L-lactic acid of 3 different MW's. Check out www.polyvivo.com to learn more.

New Products

2010-11-18T09:38:00.003-05:00

The PST division of Akina is presenting some new products this week. First we have a set of normal straight chain P(D,L)La to add to the PLGA for those who are after the normal, non-block polymer versions of these products. Unlike every other provider on the market today we have no minimal order so you can buy as much or as little as you like. Also unlike other providers click on the product name and you will see a complete Certificat of Analysis. Our COA's include the GPC and HNMR results from that that exact batch of material so you see all information and full characterization.

On the other end of the spectrum, due to its immense popularity as a custom synthesis product, we are proud to present for the first time as a stock product AI03 which is a Maleimide endcapped (PEG terminus) diblock copolymer Mal-PEG-PLGA. The maleimide affords flexibility as it reacts with thiol units to bond strongly to peptides and other ligands allowing you to decorate the micelle for targeting to specific cells. This particular one is a fairly short-chain 3000Da PEG-5000Da PLGA however other molecular weights can be made on demand and we are looking forward to expanding this product line as well to include other weights.

Biodegradable Polymers Overview

2010-11-16T13:29:00.001-05:00

Link below leads to a presentation regarding biodegradable polymers with a very good general overview. An excellent starting point for one interested in learning more about this field.

Presented by Caiping Lin Nov 29, 2005 at Chemical Dept. College of Environmental Science and Forestry State University of New York.
http://www.phy.syr.edu/~lmovilea/BiodegradablePolym.pdf

Biodegradable Polymer Overview

2010-11-16T13:26:00.001-05:00

The below article gives an excellent overview of biodegradable polymers and their biomedical usage. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"This paper reviews biodegradable synthetic polymers focusing on their potential in tissue engineering applications. The major classes of polymers are briefly discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are indicated based on studies reported in the literature. A vast majority of biodegradable polymers studied belongs to the polyester family, which includes polyglycolides and polylactides. Some disadvantages of these polymers in tissue engineering applications are their poor biocompatibility, release of acidic degradation products, poor processability and loss of mechanical properties very early during degradation. Other degradable polymers such as polyorthoesters, polyanhydrides, polyphosphazenes, and polyurethanes are also discussed and their advantages and disadvantages summarised. With advancements in tissue engineering it has become necessary to develop polymers that meet more demanding requirements. Recent work has focused on developing injectable polymer compositions based on poly (propylene fumarate) and poly (anhydrides) to meet these requirements in orthopaedic tissue engineering. Polyurethanes have received recent attention for development of degradable polymers because of their great potential in tailoring polymer structure to achieve mechanical properties and biodegradability to suit a variety of applications."

P.A. Gunatillake, R. Adhikari, Biodegradable synthetic polymers for tissue engineering. Cells and Materials 5 (2003) 1-16.

Link to full-text:
http://www.ecmjournal.org/journal/papers/vol005/pdf/v005a01.pdf

Custom Pegylation

2010-11-16T13:23:00.002-05:00

PEG has great biocompatibility and can increase residence time of a variety of proteins/peptides. One of Akina’s custom synthesis options is coupling of PEG or other stabilizing agents to the protein/peptide of your choice. Contact John Garner (jg@akinainc.com) to learn how Akina can help you increase your peptides residence time.

The below article discusses the usage of pegylation to increase the residence time of a model BSA peptide. Go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"Methoxypolyethylene glycols of 1900 and 5000 daltons have been attached covalently to bovine serum albumin using cyanuric chloride as the coupling agent. When sufficient polymer is attached, the modified bovine serum albumin appears to lose its immunogenicity in the rabbit and, on intramuscular or intravenous injection, elicits antibodies neither to itself nor to native bovine serum albumin. It does not react with antibodies raised against native bovine serum albumin. Bovine serum albumin to which methoxypolyethylene glycol has been attached exhibits a blood circulating life in the rabbit rather similar to native bovine serum albumin, except that it is not removed from circulation by the eventual development of antibodies. Modified bovine serum albumins which had been iodinated with 125I, or prepared with [14C]cyanuric chloride, were injected intravenously in rabbits. Both labels appeared almost quantitatively in the urine after 30 days. The modified bovine serum albumins showed substantial changes in properties, such as solubility, electrophoretic mobility in acrylamide gel, ion exchange chromatography, and sedimentation, as compared with the unmodified protein."

A. Abuchowski, T. van Es, N.C. Palczuk, F.F. Davis, Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. Journal of Biological Chemistry 252(11) (1977) 3578-3581.

Full-Text: http://www.jbc.org/content/252/11/3578.full.pdf+html

Micelle Formation Theory

2010-11-16T13:18:00.003-05:00

The following articles describe micelle formation and theoretical aspects. Note several PolyVivo products are capable of forming micelles for drug delivery and other uses. Go to www.polyvivo.com to find out more. Go to original source or links below for full-text of these articles. Abstract follows:

"We predict, qualitatively, the structural transitions in microemulsion systems induced by nonionic polymers, by virtue of their ability to associate with the surfactant assemblies. The predictions are made possible by linking (a) theoretical calculations of the domains of existence of oil-in-water (O/W) and water-in-oil (W/O) droplet microemulsions with (b) the experimental observation that on increasing the alcohol-to-surfactant ratio, an O/W droplet microemulsion phase inverts to a W/O droplet microemulsion, often via a bicontinuous microemulsion. We predict five distinct types of polymer-induced structural transitions: (I) an OIW droplet microemulsion remains an O/W droplet system but the amount of oil solubilized and the radius of the droplet are both reduced; (11) a bicontinuous microemulsion transforms into an O/W droplet microemulsion; (111) a WIO droplet microemulsion inverts to an O/W droplet microemulsion with the droplet radius either decreasing in size (IIIA) or increasing in size (IIIB); (IV) a WIO droplet microemulsion transforms into a bicontinuous microemulsion; (V) a WIO droplet microemulsion remains a W/O system but the droplet radius and the amount of water solubilized are both increased. We also predict that the addition of polymers cannot lead to the following types of transitions: (VI) an OIW droplet microemulsion cannot invert to a W/O droplet microemulsion; (VII) an 01 W droplet microemulsion cannot transform into a bicontinuous microemulsion; (VIII) a bicontinuous microemulsion cannot transform into a W/O droplet microemulsion. From a practical point of view, the above predictions open up aneffective approach to the manipulation of microemulsion structures using nonionic-polymer molecules as additives. "
R. Nagarajan, Polymer-induced structural transitions in microemulsions. Langmuir 9(2) (1993) 369-375. (full-text: http://www.personal.psu.edu/faculty/r/x/rxn/1993-Langmuir-9-p369-375.pdf)

"A thermodynamic model for surfactant binding to polymers in dilute aqueous solution is present. It assumes that the inter- molecular contacts between the polar and the non-polar polymer segment resemble the macroscopic hydrocarbon-water interface ,where preferential accumulation of surfactant accurs. The model also considers the competitive surfactant micelization."
R. Nagarajan, Thermodtnamics of surfactant-polymer interactions in dilute aqueous solutions. Chemical Physics Letters 76(2) (1980) 282-286. (full-text: http://www.personal.psu.edu/faculty/r/x/rxn/1980-Chem%20Phys%20Lett-76-p282-286.doc)

Block copolymer micellization

2010-11-16T13:16:00.001-05:00

The below article discusses the usage of block copolymers for micellization in a very general overview. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"This article deals with recent progress including the author's work in the field of block copolymer self-assembly in solution and on solid surfaces. The synthesis methods for producing block copolymers with well-defined structures, molecular weights and composition are outlined with emphasis on ionic and controlled free radical polymerization techniques. A general overview of the preparation, characterization and theories of block copolymer micellar systems is presented. Selected examples of micelle formation in aqueous and organic medium are given for di- and triblock copolymers, as well as for block copolymers with more complex architectures. Current and potential application possibilities of block copolymer colloidal assemblies as stabilizers, flocculants, nanoreservoir in, among others, controlled delivery of bioactive agents, catalysis, latex agglomeration and stabilization of non-aqueous emulsion are also discussed."

G. Riess, Micellization of block copolymers. Progress in Polymer Science 28(7) (2003) 1107-1170.

Full-text
http://www.eng.buffalo.edu/Courses/ce435/Riess03.pdf

PEG-PCL micelles

2010-11-16T13:14:00.001-05:00

The below article discusses the usage of diblock PEG-PCL for formulation of micelles. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

The polymerization of ε−caprolactone (CL) in the presence of HCl · Et2O via activated monomer mechanism was performed to synthesize diblock copolymers composed of methoxy polyethyleneglycol (MPEG) and poly(ε−caprolactone) (PCL). The obtained PCLs had molecular weights close to the theoretical values calculated from the CL to MPEG molar ratios and exibited monomodal GPC curves. We successfully prepared MPEG and PCL diblock copolymers by activated monomer mechanism. The micellar characterization of MPEG-PCL diblock copolymers in an aqueous phase was carried out by using NMR, dynamic light scattering, AFM and fluorescence techniques. The diblock copolymers formed micelles with a critical micelle concentration (CMC) ranging 2.07 x 10-2 - 1.16 x 10-3 mg/mL depended on the block lengths of diblock copolymers. The diameters of micelles, measured by dynamic light scattering, were100-250 nm. Most micelles exhibited a spherical shape in AFM.

M.S. Kim, H. Hyun, Y.H. Cho, K.S. Seo, W.Y. Jang, S.K. Kim, G. Khang, H.B. Lee, Preparation of methoxy poly(ethyleneglycol)-block-poly(caprolactone) via activated monomer mechanism and examination of micellar characterization. Polymer Bulletin 55(3) (2005) 149-156.

FullText:
http://www.springerlink.com/content/j0206u842571rx4m/

PLA-PEG-PLA hydrogels

2010-11-16T13:12:00.001-05:00

The below article discusses the usage of PLA-PEG-PLA hydrogels for tissue engineering. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"Polymeric materials are important in many medical applications. Regenerative medicine offers the potential to repair or replace damaged tissue and polymers are an essential component of many tissue engineering approaches. Hydrogels have many advantageous properties but, generally, lack robust mechanical properties. At the same time, mounting evidence points to the importance of the matrix modulus when constructing devices. In this context, triblock copolymers made from poly(L-lactide)–poly(ethylene glycol)–poly(L-lactide) have been prepared and formulated into hydrogels. Investigations into their mechanical properties found the elastic modulus to be greater than 10 kPa which is at least one order of magnitude stiffer than previously reported from macromolecules composed of similar monomers. Part of the reason is the presence of crystalline lactide domains. Creating hydrogels with tailored modulus across the kPa range will likely have important ramifications in regenerative medicine."

G.N. Tew, N. Sanabria-DeLong, S.K. Agrawal, S.R. Bhatia, New properties from PLA–PEO–PLA hydrogels. Soft Matter 1 (2005) 253–258.

full text:
http://www.pse.umass.edu/gtew/images/Tew-SoftMatter-2005-253.pdf

PEG/PLGA block copolymers thermogelation

2010-11-16T13:09:00.001-05:00

The below article discusses the usage of PEG/PLGA thermosensitive polymers for drug delivery. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"The aqueous solutions of poly(ethylene glycol) grafted with poly(lactic acid-co-glycolic acid) flow freely at room temperature but form gels at higher temperature. The existence of micelles in water at low polymer concentration was confirmed by cryo-transmission electron microscopy and dye solubilization studies. The micellar diameter is about 9 nm, and the critical micelle concentration is in a range of 0.01-0.05 wt %. The critical gel concentration, above which a gel phase appears, was 16 wt %, and the sol-to-gel transition temperature was slightly affected by the concentration between 16 and 25 wt %. At sol-to-gel transition, viscosity and modulus increased abruptly, and 13C NMR showed molecular motion of hydrophilic poly(ethylene glycol) backbones decreased while that of hydrophobic poly(lactic acid-coglycolic acid) side chains increased. The hydrogel of PEG-g-PLGA with hydrophilic backbones was transparent during degradation and remained a gel for 1 week, suggesting a promising material for shortterm drug delivery."

B. Jeong, M.R. Kibbey, J.C. Birnbaum, Y.-Y. Won, A. Gutowska, Thermogelling Biodegradable Polymers with Hydrophilic Backbones: PEG-g-PLGA. Macromolecules 33(22) (2000) 8317-8322.

link to full-text
http://cobweb.ecn.purdue.edu/~yywon/publications/2000%20Macromolecules%2033(22)%208317-8322%20Thermogeling%20Biodegradable.pdf

Block copolymers thermogelation

2010-11-16T13:07:00.002-05:00

The below article shows the usage of thermosensitive block polymers for depot formation. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

Aqueous solutions of poly(dl-lactic acid-co-glycolic acid)-g-poly(ethylene glycol) copolymers exhibited sol-to-gel transition with increasing temperature. Further increase in temperature makes the system flow and form a sol phase again. Subcutaneous injection of a copolymer aqueous solution (0.5 mL) resulted in a formation of a hydrogel depot by temperature-sensitive sol-to-gel transition in a rat model. The reliable determination and control of sol-to-gel transition temperatures are the most important issues for this kind of sol−gel reversible hydrogel. The sol-to-gel transition temperature determined by the test tube inverting method, falling ball method, and dynamic mechanical analysis coincided within 1−2 °C. Fine tuning of the sol-to-gel transition temperature was achieved by varying the ionic strength of the polymer solutions and by mixing two polymer aqueous solutions with different sol-to-gel transition temperatures. The sol-to-gel transition temperature of polymer mixture aqueous solutions was well described by an empirical equation of miscible blends, indicating miscibility of the two polymer systems in water on the molecular level.

Y.-M. Chung, K.L. Simmons, A. Gutowska, B. Jeong, "Sol-Gel Transition Temperature of PLGA-g-PEG Aqueous Solutions. Biomacromolecules 3(3) (2002) 511-516.

http://pubs.acs.org/doi/abs/10.1021/bm0156431

Diblock copolymers thermogelation

2010-11-16T13:04:00.002-05:00

The below article describes diblock copolymers and thermogelation. Find these polymers at www.polyvivo.com, go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"Diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and poly(ϵ-caprolactone) (PCL), poly(δ-valerolactone) (PVL), poly(L-lactic acid) (PLLA), or poly(lactic-co-glycolic acid) (PLGA) as biodegradable polyesters were prepared to examine the phase transition of diblock copolymer solutions. MPEG–PCL and MPEG–PVL diblock copolymers and MPEG–PLLA and MPEG–PLGA diblock copolymers were synthesized by the ring-opening polymerization of ϵ-caprolactone or δ-valerolactone in the presence of HCl · Et2O as a monomer activator at room temperature and by the ring-opening polymerization of L-lactide or a mixture of L-lactide and glycolide in the presence of stannous octoate at 130 °C, respectively. The synthesized diblock copolymers were characterized with 1H NMR, IR, and gel permeation chromatography. The phase transitions for diblock copolymer aqueous solutions of various concentrations were explored according to the temperature variation. The diblock copolymer solutions exhibited the phase transition from gel to sol with increasing temperature. As the polyester block length of the diblock copolymers increased, the gel-to-sol transition moved to a lower concentration region. The gel-to-sol transition showed a dependence on the length of the polyester block segment. According to X-ray diffraction and differential scanning calorimetry thermal studies, the gel-to-sol transition of the diblock copolymer solutions depended on their degrees of crystallinity because water could easily diffuse into amorphous polymers in comparison with polymers with a crystalline structure. The crystallinity markedly depended on both the distinct character and composition of the block segment."

M.S. Kim, K.S. Seo, G. Khang, S.H. Cho, H.B. Lee, Preparation of methoxy poly(ethylene glycol)/polyester diblock copolymers and examination of the gel-to-sol transition. Journal of Polymer Science Part A: Polymer Chemistry 42(22) (2004) 5784-5793.

http://dx.doi.org/10.1002/pola.20430

PLGA-PEG-PLGA gene delivery

2010-11-16T12:58:00.002-05:00

The below article shows the usage of PLGA-PEG-PLGA thermosensitive polymers for gene delivery. Find these polymers at www.polyvivo.com go to the link below or to the original source for full-text for the article. (note the below article did not not necessarily use an Akina product for this research). Abstract follows:

"Purpose. Microneedles disrupt the stratum corneum barrier layer of skin creating transient pathways for the enhanced permeation of therapeutics into viable skin regions without stimulating pain receptors or causing vascular damage. The cutaneous delivery of nucleic acids has a number of therapeutic applications; most notably genetic vaccination. Unfortunately non-viral gene expression in skin is generally inefficient and transient. This study investigated the potential for improved delivery of plasmid DNA (pDNA) in skin by combining the microneedle delivery system with sustained release pDNA hydrogel formulations. Materials and Methods. Microneedles were fabricated by wet etching silicon in potassium hydroxide. Hydrogels based on Carbopol polymers and thermosensitive PLGA-PEG-PLGA triblock copolymers were prepared. Freshly excised human skin was used to characterise microneedle penetration (microscopy and skin water loss), gel residence in microchannels, pDNA diffusion and reporter gene (b-galactosidase) expression. Results. Following microneedle treatment, channels of approximately 150–200 mm depth increased trans-epidermal water loss in skin. pDNA hydrogels were shown to harbour and gradually release pDNA. Following microneedle-assisted delivery of pDNA hydrogels to human skin expression of the pCMVb reporter gene was demonstrated in the viable epidermis proximal to microchannels. Conclusions. pDNA hydrogels can be successfully targeted to the viable epidermis to potentially provide sustained gene expression therein. "

M. Pearton, C. Allender, K. Brain, A. Anstey, C. Gateley, N. Wilke, A. Morrissey, J. Birchall, Gene Delivery to the Epidermal Cells of Human Skin Explants Using Microfabricated Microneedles and Hydrogel Formulations. Pharmaceutical Research 25(2) (2008) 407-416.

http://www.tyndall.ie/research/mems/pubs/Pearton%20-%20Gene%20Delivery%20to%20the%20Epidermal%20Cells%20of%20Human%20Skin%20Explants%20Using%20Microfabricated%20Microneedles%20and%20Hydrogel%20Formulations.pdf

PLA-PEG thermogel

2010-11-16T12:55:00.002-05:00

The below study highlights the capabilities for PLA and PEG copolymers to be used for drug delivery thermogel. Check out http://www.polyvivo.com to learn more. (note the below study did not necessarily use a PolySciTech product(s)). Please go to original source for fultext or follow the link below. Abstract follows:

"Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide5,6 and poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel–sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 °C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs."

B. Jeong, Y.H. Bae, D.S. Lee, S.W. Kim, Biodegradable block copolymers as injectable drug-delivery systems. Nature 388(6645) (1997) 860-862.
http://www.nature.com/nature/journal/v388/n6645/abs/388860a0.html

Flamma Fluor Attachment Moeity

2010-11-16T12:40:00.003-05:00

The below is an email chain from a customer's question regardinig structure and attachment of flamma fluor dye. To learn more about Flamma dyes see (http://www.akinainc.com/flamma-fluor.html). The below links lead to full-text scholarly articles regarding protein attachment via the vinyl sulfone functional group. For confidentiality, the customers name is not included here.

------------------
"Quoting John Garner :

Dear (Customer),
Attached are the chemical structures for these dyes[FG-456, FR-648]. These also use a vinyl sulfone group which binds to amines and thiols depending on conditions. Below are a couple of links for how vinyl sulfone binds to proteins (the papers below are not for staining but for other purposes however the same principles apply)

http://med.stanford.edu/bogyolab/pdf/9653549.pdf

http://www.pnas.org/content/96/18/10403.long

http://www.pnas.org/content/98/6/2967.full

Hope this helps,
John "

PolySciTech Facebook Page

2010-11-10T11:29:00.002-05:00

Flamma Fluor Quantum Yield

2010-11-08T16:07:00.003-05:00

Protein delivery via PEG-PLA

2010-11-05T13:55:00.002-04:00

The below study highlights the capabilities for PEG-PLA to be used for delivery of protein based BMP molecules. Check out http://www.polyvivo.com to learn more. (note the below study did not necessarily use a PolySciTech product(s)). Please go to original source for fultext or follow the link below. Abstract follows:

Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. To find new synthetic absorbable polymers with plastic nature that can be used as BMP-carrier materials, six types of poly-D,L-lactic acid-polyethylene glycol block copolymer (PLA-PEG) with various molecular weights of PLA and PEG were synthesized. These were PLA6,500-PEG3,000 (P-1), PLA11,500-PEG3,000 (P-2), PLA17,500-PEG3,000 (P-3), PLA6,500-PEG1,000 (P-4), PLA15,000-PEG8,000 (P-5), and PLA8,500-PEG1,000 (P-6). Fifty milligrams of these polymers was mixed with 0 μg (control) or 5, 10, or 20 μg of recombinant human BMP-2 (rhBMP-2). These pellets were implanted into the dorsal muscle pouches of 144 mice (six pellets consisting of the same polymer and dose of rhBMP-2 for a specific group). Three weeks after surgery, the pellets were harvested and examined by radiographic and histological methods. All P-1 pellets with 10 or 20 μg of rhBMP-2 showed bone formation with hematopoietic marrow and bony trabeculae, as did one third of those with 5 μg of rhBMP-2. The incidence of new bone formation with P-2 pellets or that of P-5 pellets was lower than that of P-1 pellets. No bone was formed in any other type of pellet. These results indicated that the PLA6,500-PEG3,000 polymer with plastic properties was found to work well as a BMP carrier.

N. Saito, T. Okada, S. Toba, S. Miyamoto, K. Takaoka, New synthetic absorbable polymers as BMP carriers: Plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers. Journal of Biomedical Materials Research 47(1) (1999) 104-110.
http://dx.doi.org/10.1002/(SICI)1097-4636(199910)47:1<104::aid-jbm15>3.0.CO;2-7

Protein Adsorbtion for diblock PEG-PLGA/PLA

2010-11-05T13:51:00.003-04:00

The below study highlights the capabilities for dilock PEG-PLGA/PLA to be used for controlling protein adsorption/cellular behavior on surfaces. Check out http://www.polyvivo.com to learn more. (note the below study did not necessarily use a PolySciTech product(s)). Please go to original source for fultext or follow the link below.

abstract:
The adhesion of marrow stromal osteoblasts and the adsorption of fetal bovine serum (FBS) proteins to end-capped poly(D,L-lactic acid) 50:50 (PLA50) of molecular weight 17,000 (PLA5017), non-end-capped PLA50 of molecular weight 11,000 (PLA5011h), and a diblock copolymer made of poly(ethylene glycol)-monomethyl ether of molecular weight 5,000 and PLA50 of molecular weight 20,000 (Me.PEG5–PLA20) were investigated. Cell attachment and proliferation on both PLA50 polymers were equally good. The block copolymer did not allow the proliferation of cells. However, the attached cells were highly differentiated and metabolically active in contrast to the cells on PLA50. Moreover, surface analysis studies using electron spectroscopy revealed that FBS proteins adsorbed well from aqueous solutions to the PLA50 surfaces while they adsorbed substantially less to the block copolymer. These results suggest that Me.PEG-PLA block copolymers may be used to regulate protein adsorption and, therefore, cell adhesion by varying the block composition of the copolymer.

http://dx.doi.org/10.1002/(SICI)1097-4636(19990905)46:3<390::aid-jbm12>3.0.CO;2-N

Degradation Rate

2010-11-05T13:43:00.002-04:00

The below study elucidates the relative degradation rates of block copolymers with respect to their PEG-PLGA content. Check out http://www.polyvivo.com to learn more. (note the below study did not necessarily use a PolySciTech product(s). Please go to original source for fultext or follow the link below.)

The degradation behaviour of a new class of multi-block copolymers containing poly( -lactic-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) segments was studied under conditions mimicking those found in biological fluids. The dissolution times of the new PLGA-PEG multi-block copolymers mainly depend on the length of the PEG segments present in their structure, i.e., on their PEG content on a weight/weight basis. At higher PEG contents, partially degraded PLGA segments are brought in solution by attached PEG segments. In all cases, the dissolution rates decrease by increasing the total surface area of the specimens tested.

M. Penco, S. Marcioni, P. Ferruti, S. D'Antone, R. Deghenghi, Degradation behaviour of block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments. Biomaterials 17(16) (1996) 1583-1590.
http://www.sciencedirect.com/science/article/B6TWB-3VSG9R5-5/2/ad9da8d0d782c21fcbc1b8ece8123688

Clinical Studies - Block Copolymers

2010-11-04T16:19:00.002-04:00

A common question about block copolymers is are they in any current drug delivery formulations. The answer to that is that these copolymers are not in any FDA approved USA material yet however they have shown promise in clinical studies. There are currently clinical studies underway for Genexol system which delivers paclitaxel using a block copolymer of PEG-PLA. Similar block copolymers can be purchased from www.polyvivo.com

"ABSTRACT
Purpose: The rationale for developing an alternative
paclitaxel formulation concerns Cremophor EL-related side
effects, and a novel paclitaxel delivery system might augment
its therapeutic efficacy. Genexol-PM is a polymeric
micelle formulated paclitaxel free of Cremophor EL. A
phase I study was performed to determine the maximum
tolerated dosage, dose-limiting toxicities, and the pharmacokinetic
profile of Genexol-PM in patients with advanced,
refractory malignancies.
Experimental Design: Twenty-one patients were entered
into the study. Genexol-PM was i.v. administered over 3 h
every 3 weeks without premedication. The Genexol-PM dose
was escalated from 135 mg/m2 to 390 mg/m2.
Results: All of the patients were evaluable for toxicity
and response. Acute hypersensitivity reactions were not observed.
Neuropathy and myalgia were the most common
toxicities. During cycle 1, grade 3 myalgia occurred in 1
patient at 230 and 300 mg/m2, respectively. At 390 mg/m2, 2
of 3 patients developed grade 4 neutropenia or grade 3
polyneuropathy. Therefore, the maximum tolerated dosage
was determined to be 390 mg/m2. There were 3 partial
responses (14%) among the 21 patients. Of the 3 responders,
2 were refractory to prior taxane therapy. The paclitaxel
area under the curve from time 0 to infinity and peak or
maximum paclitaxel concentration seemed to increase with
escalating dose, except at 230 mg/m2, which suggests that
Genexol-PM has linear pharmacokinetics.
Conclusion: The main dose-limiting toxicities were neuropathy,
myalgia, and neutropenia, and the recommended
dosage for a phase II study is 300 mg/m2. Genexol-PM is
believed to be superior to conventional paclitaxel in terms of
the obviation of premedication and the delivery of higher
paclitaxel doses without additional toxicity. "

T.-Y. Kim, D.-W. Kim, J.-Y. Chung, S.G. Shin, S.-C. Kim, D.S. Heo, N.K. Kim, Y.-J. Bang, Phase I and Pharmacokinetic Study of Genexol-PM, a Cremophor-Free, Polymeric Micelle-Formulated Paclitaxel, in Patients with Advanced Malignancies Clin Cancer Res (2004). (link to full-text http://clincancerres.aacrjournals.org/content/10/11/3708.full.pdf+html)

PLGA-PEG-PLGA triblock thermogel

2010-11-01T09:48:00.001-04:00

The below study highlights the capabilities for PLGA-PEG-PLGA to be used for drug delivery thermogel. Check out http://www.polyvivo.com to learn more about these types of polymers. (note the below study did not necessarily use a PolySciTech product(s)).

"Injectable biodegradable temperature-responsive poly(dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with dl-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of dl-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of dl-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of dl-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of dl-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 [mu]g/ml, 25 °C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency."

M. Qiao, D. Chen, X. Ma, Y. Liu, Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: Synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels. International Journal of Pharmaceutics 294(1-2) (2005) 103-112. http://www.sciencedirect.com/science/article/B6T7W-4FM01FH-2/2/c45e29a956179c5b82a3c47701f8405f

"ugly" polymers - appearance

2010-10-29T12:16:00.002-04:00

One FAQ we get all the time is why our material looks like a wad of polymer rather than a fine dust or pellets. Dust and pellets require grinding/extruding and we generally do not expose our polymers to that kind of heat/friction especially since they are delicate. The "wad" is the polymer appearance as it was removed from precipitation purification or as it was redissolved/filtered/vacuum dried from an organic solvent. If you really need a dust or pellets for your application you can request this, but we don't normally do this as heat and friction can cause some damage to degradable polymers.

PEG-PLGA usage

2010-10-26T11:52:00.001-04:00

The below study highlights the capabilities for PEG-PLGA to be used for drug delivery nanoparticles. Check out http://www.polyvivo.com to learn more about these types of polymers. (note the below study did not necessarily use a PolySciTech product(s)).

"PEG content from 0.5 to 20 wt %, a PEG content between 2 and 5 wt % was determined as a threshold value for optimal protein resistance. When increasing the PEG content in the nanoparticles above 5 wt % no further reduction in protein adsorption was achieved. Phagocytosis by PMN studied using chemiluminescence and zeta potential data agreed well with these findings: the same PEG surface density threshold was found to ensure simultaneously efficient steric stabilization and to avoid the uptake by PMN cells. Supposing all the PEG chains migrate to the surface, this would correspond to a distance of about 1.5 nm between two terminally attached PEG chains in the covering ‘brush’. Particles from PEG5K-PLA45K, PEG5K-PLGA45K and PEG5K-PCL45K copolymers enabled to study the influence of the core on plasma protein adsorption, all other parameters (corona thickness and density) being kept constant. Adsorption patterns were in good qualitative agreement with each other. Only a few protein species were exclusively present just on one type of nanoparticle. However, the extent of proteins adsorbed differed in a large extent from one particle to another. In vivo studies could help elucidating the role of the type and amount of proteins adsorbed on the fate of the nanoparticles after intraveinous administration, as a function of the nature of their core. These results could be useful in the design of long circulating intravenously injectable biodegradable drug carriers endowed with protein resistant properties and low phagocytic uptake. "

R. Gref, M. Lück, P. Quellec, M. Marchand, E. Dellacherie, S. Harnisch, T. Blunk, R.H. Müller, [`]Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids and Surfaces B: Biointerfaces 18(3-4) (2000) 301-313.
http://www.sciencedirect.com/science/article/B6TFS-40T9J4H-D/2/7f6343d21452368fcae44f7f1a2ced7b

diblock PEG-PLGA usage note

2010-10-26T11:50:00.001-04:00

Diblock PEG-PLGA usage note

2010-10-26T11:44:00.004-04:00

The below study highlights the capabilities for PEG-PLGA to be used for drug delivery nanoparticles. Check out http://www.polyvivo.com/ to learn more about these types of polymers. (note the below study did not necessarily use a PolySciTech product(s)).

"The development of long-circulating carriers capable of continuously delivering drugs intravenously provides a potential approach to achieve targeting of drugs to specific sites of action. In this research, polyethylene glycol (PEG)-coated nanospheres were prepared in a single step process using amphiphilic diblock and multiblock copolymers, and their drug encapsulation properties and release characteristics were investigated in vitro. The results obtained indicate that the parameters controlling drug release characteristics of these nanospheres are the chemical composition of their hydrophobic core (i.e. polyester or polyanhydride), as well as the molecular weight and surface density of their hydrophilic (i.e. PEG) chains"

M.T. Peracchia, R. Gref, Y. Minamitake, A. Domb, N. Lotan, R. Langer, PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: Investigation of their drug encapsulation and release characteristics. Journal of Controlled Release 46(3) (1997) 223-231. http://www.sciencedirect.com/science/article/B6T3D-3V2MYFP-1X/2/c7d6d5f390fc991fc9e3c0cee685810a

PEG-PCL drug delivery nanoparticles

2010-10-21T22:25:00.003-04:00

The below study highlights the capabilities for PEG-PCL for drug delivery nanoparticles. Check out www.polyvivo.com to learn more about these types of polymers. (note the below study did not necessarily use a PolySciTech product).

"To establish a satisfactory delivery system for local delivery of Tetradrine (Tet), four kinds of core-shell nanoparticles were prepared from di-block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (MePEG-PCL) and tri-block copolymer of polycaprolactone-poly(ethylene glycol)-polycaprolactone (PCL-PEG-PCL). The physiochemical traits of the four kinds of nanoparticles including morphology, particle size, zeta-potential, drug-loading content, stability, and in vitro release profile were studied. We also evaluated the four kinds of nanoparticles by in vitro cellular uptake experiment, cytotoxicity assay against LoVo cells, and biocmpatibility study. Histoculture Drug Response Assay (HDRA), a more predictive method usually used to evaluate chemosensitivity was firstly applied in our study to evaluate the antitumor potency of polymeric nanoparticles. The current study showed that all the four kinds of copolymers exhibited remarkable in vitro antitumor effects, especially in HDRA assay. The configuration and composition of the copolymers were important for the properties and functions of the nanoparticles. Nanoparticles prepared from the di-block copolymer with a particle size around 300 nm and the hydrophobic composition about 80% was determined as the most effective drug carrier for further studies."

R. Li, X. Li, L. Xie, D. Ding, Y. Hu, X. Qian, L. Yu, Y. Ding, X. Jiang, B. Liu, Preparation and evaluation of PEG-PCL nanoparticles for local tetradrine delivery. International Journal of Pharmaceutics 379(1) (2009) 158-166. http://www.sciencedirect.com/science/article/B6T7W-4WH8C7F-3/2/81fc59a2809df426504d9a2173d1e0ba

PEG-PCL biocompatibilty

2010-10-21T21:55:00.004-04:00

The study below highlights some of the capabilities of polyethylene glycol block for improving biocompatibility of the polymer. Check out www.polyvivo.com to learn more.(note the below study was not necessarily performed using a PolySciTech product).

"In this study, we prepared diblock copolymers of poly([var epsilon]-caprolactone) (PCL) and poly(ethylene glycol) (PEG) by aluminum alkoxide catalysts. The biological responses to the spin cast surface of different PCL/PEG diblock copolymers were investigated in vitro. Our results showed that surface hydrophilicity improved with the increased PEG segments in diblock copolymers and that bacteria adhesion was inhibited by increased PEG contents. PCL-PEG 23:77 showed nanotopography on the surface. The number of adhered endothelial cells, platelets and monocytes on diblock copolymer surfaces was inhibited in PCL-PEG 77:23 and enhanced in PCL-PEG 23:77. Nevertheless, the platelet and monocyte activation on PCL-PEG 23:77 was reduced. PCL-PEG 23:77 had better cellular response as well as lower degree of platelet and monocyte activation. The current study was the first one to demonstrate that surface nanotopography could influence not only cell adhesion and growth but also platelet and monocyte activation."

S.-H. Hsu, C.-M. Tang, C.C.C.-C. Lin, Biocompatibility of poly([var epsilon]-caprolactone)/poly(ethylene glycol) diblock copolymers with nanophase separation. Biomaterials 25(25) (2004) 5593-5601. http://www.sciencedirect.com/science/article/B6TWB-4BWCBWW-2/2/d44c205286fb3dafb38030138b147abb

Usage Note PEG-PCL/PEG-PLA

2010-10-21T21:50:00.003-04:00

Example of current research using diblock copolymers PEG-PCL and PEG-PLA. Check out www.polyvivo.com to learn more about how you can get some of these same type polymers.(note the research below was performed using a similar material, but not necessarily a PolySciTech product)

"Controlled release polymer vesicles are prepared using hydrolysable diblock copolymers of polyethyleneglycol-poly--lactic acid (PEG-PLA) or polyethyleneglycol-polycaprolactone (PEG-PCL). Encapsulation studies with a common anti-cancer agent, doxorubicin, show loading comparable to liposomes. Rates of encapsulant release from the hydrolysable vesicles are accelerated with an increased proportion of PEG but are delayed with a more hydrophobic chain chemistry (i.e. PCL). Rates of release also rise linearly with the molar ratio of degradable copolymer blended into membranes of a non-degradable, PEG-based block copolymer (PEG-polybutadiene (PBD)). With all compositions, in both 100 nm and giant vesicles, the average release time (from hours to days) reflects a highly quantized process in which any given vesicle is either intact and retains its encapsulant, or is porated and slowly disintegrates. Poration occurs as the hydrophobic PLA or PCL block is hydrolytically scissioned, progressively generating an increasing number of pore-preferring copolymers in the membrane. Kinetics of this evolving detergent mechanism overlay the phase behavior of amphiphiles with transitions from membranes to micelles allowing controlled release."
[1] F. Ahmed, D.E. Discher, Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles. Journal of Controlled Release 96(1) (2004) 37-53. http://www.sciencedirect.com/science/article/B6T3D-4BT1T53-1/2/88fd9757800057d8ba7e13e868bbb224

2010-10-19T16:08:00.003-04:00

A popular polymer for custom synthesis is PLGA-PEG-Maleimide. Maleimide operates well as a thiol binding domain allowing customization with your peptide chain. PolySciTech can prepare PLGA-PEG-Maleimide (or PLA, PCL blocks) to your specifications contact me at jg@akinainc.com to discuss your application.

AKPLGA-Fluorescein

2010-10-18T23:20:00.004-04:00

Do you want to "see" your PLGA? At Akina we have covalently bound Fluorescein dye to PLGA for easy microscope observations in fluorescent mode so you can track your nanoparticles where ever they may go.

Flamma Fluor P-series Question

2010-10-18T10:38:00.004-04:00

This post is from a response to a customer request. To protect their identity the customer's information has been removed:
-----------------------------
Dear (Customer),

The quantum yield for FPR-675 and FPI-749 is

FPR-675 : 0.10
FPI-749 : 0.04

These were measured relative to Rhodamin 6G standard (0.95) and are
approxiamately the same quantum yield as Cy5.5 and Cy7.5.

I have also attached here (to original email) the uneditied COAs which include structure. The vinyl-sulfone group is well reported to bind well to amines and thiols so it is a good probe for attaching to peptide based materials for immunoassays etc. The FI-749 (a.k.a. FR749) is excellent for seeing inside living
organisms as it operates well below the autofluorescence threshold and has
been experimentally proven in rats to show location of tumors when combined
with nanoparticles.

Thanks,
John Garner
------------------------------
Please note that due to contractual obligations we can not show unedited COA's for Flamma Fluor dyes (include molecular structure) on the website however these are available upon request and feel free to email jg@akinainc.com to recieve.

PEG-PLA-PEG triblock

2010-10-15T09:58:00.003-04:00

We are now offering a triblock copolymer which has PEG arms on the exterior portion as PEG-PLA-PEG. This is a non-water soluble triblock which serves as an excellent way to make PEG-decorated microparticles. Soon to come are other PEG arm triblocks. Feel free to drop a comment here and mention any MW's or types of this triblock you would be interested in

New Polyvivo available

2010-05-19T09:33:00.002-04:00

More polyvivo triblock copolymers are available including AK13-AK19. AK13 and AK15 are medium molecular weight non-water soluble triblocks for enhanced drug delivery. AK16-AK18 are non-water soluble high molecular weight triblocks. AK19 is a water soluble thermosensitive triblock for aquoes delivery.

2010-05-19T09:30:00.002-04:00

New Fluorescent dyes are available. These dyes are the "P" series which are highly reactive to amine groups and can be used to label proteins and antibodies for biological studies. Learn more about the P series dyes at http://www.akinainc.com/pdf/flamma_p.pdf and see our catalogue at http://www.akinainc.com/flamma-fluor.html for more.

Polymer AK12 appearance - Usage

2010-03-02T09:58:00.004-05:00

I've been getting alot of questions about this one so I'll put some clarification here. PolyVivo AK12 (PLGA-PEG-PLGA ~1000-1000-1000) when it is dry state appears to be a gelatinous material. It is not diluted with anything, this is its normal appearance. It is very sticky and viscous when in dry state at room temperature. At -20C it is hard as glass and nearly impenetrable to most spatula's. It is suggested to warm the bottle gently (few minutes in 37C incubator) prior to transfer as it will be fluid enough in dry state at 37C to be scooped into another vial. It is not suggested that you store the bottle at 37C as long-term storage at this temperature could damage the polymer, only warm to 37C prior to transfer and try to do this as few times as possible to avoid polymer damage.

When this polymer is dissolved in water or saline at roughly 20% w/v solution it will act as a thermoreverse gelator. Dissolves best at 4C (refrigerator) temperature typically overnight or over a few days and then use for your purpose. When warmed the solution will gel. Gelation is optimal at room temperature (20-25C). The polymer tends to solidify at 37C and after a short time will release the water and return to solid polymer.

Flamma Fluor In-Vivo usage

2010-01-08T23:22:00.003-05:00

Image shows In-Vivo rat data with a nanosystem using both traditional rhodamine and Flamma Fluor FR-749 dye. Note Flamma Fluor operates well at 780 nm wavelength, which is longer than the wavelength of auto-fluorescence from vivo sources. This eliminated background noise from autofluorescence off the rat and allows the tumors to be identified. Images courtesy of Dr. Tonglei Li at Univeristy of Kentucky and used with permission.

PolyVivo FAQ

2009-12-07T10:28:00.000-05:00

From: http://www.akinainc.com/polymer-FAQ.html

Technical FAQ
Technical FAQ 1. Will your polymer(s) work for my application?
Answer: By far this is the most common question. The honest answer is that without great detailed information about your application, and in some cases even with great detailed information about your application, we cannot tell you for certain. The polymers you see below are utilized for medical and biochemical research. Popular applications include micelles, thermoreversible gels, and solid formulations (coating, nanoparticles, etc.). Another popular application which includes all of the previously mentioned ones is delivery of a drug. By no means are these the only applications, groundbreaking research is being performed on these polymers daily and so applications of these polymers are continually expanding. Recent research utilizing these types of polymer for these various applications can be found below in the Applications section.

Technical FAQ 2. PLA, PLGA, PEG, biodegra…what? I’m a specialist in (insert field here) but I need to start from scratch on these polymers.
The polymers listed below are utilized for biomedical implants and drug delivery. These polymers include two main types of units, biodegradable and water soluble:
Biodegradable UnitBiodegradable units include lactic, glycolic, and caprolactone units have ester linkages which react with water forming soluble acids. These acids are either metabolized or harmlessly flushed away in a normal mammalian body. See the following links for more details on biodegradable polymers:
http://www.devicelink.com/mpb/archive/98/03/002.html http://physics.syr.edu/~lmovilea/BiodegradablePolym.pdf http://www.ecmjournal.org/journal/papers/vol005/pdf/v005a01.pdf
The rate of biodegradation of these polymers generally follows the pattern:
Fastest degradation PLGA < P(D,L)LA < P(L)LA << PCL Slowest degradation
Water Soluble UnitThe water soluble unit in each case includes poly(ethylene glycol)(PEG). PEG is noted for good biocompatibility with a low immunogenic response (See: http://www.jbc.org/cgi/reprint/252/11/3578). Although PEG is not biodegradable on any meaningful timescale, it can be screened out of the body by the kidneys and excreted as long as its molecular weight is less than 10,000 Da*. These units compromise one or more blocks depending on whether the polymer is a diblock (one polyethylene glycol arm and one biodegradable arm) or a triblock (two biodegradable arms on either side of the polyethylene glycol arm).

Technical FAQ 3. Have these polymers (or similar ones) been involved in any clinical trials yet?
Yes, there are currently clinical trials underway utilizing PEG-PLA as a means to deliver Genexol-PM. See: http://clincancerres.aacrjournals.org/cgi/reprint/10/11/3708

Technical FAQ 4. Are these cGMP?
No, the polymers provided are strictly for research purposes. To the best of our knowledge, there are not yet any commercial cGMP sources of these polymers.

Applications
The potential applications of these materials are far too broad to cover here. What follows are general references and links to information regarding each application. Hopefully this information will be useful in deciding if these polymers will work for your application.
1. Micelles
Theoryhttp://www.personal.psu.edu/faculty/r/x/rxn/1980-Chem%20Phys%20Lett-76-p282-286.doc http://www.personal.psu.edu/faculty/r/x/rxn/1989-J%20Chem%20Phys-90-p1980-1994.pdf http://www.personal.psu.edu/faculty/r/x/rxn/1989-J%20Chem%20Phys-90-p1980-1994.pdf http://www.personal.psu.edu/faculty/r/x/rxn/1993-Langmuir-9-p369-375.pdf http://www.eng.buffalo.edu/Courses/ce435/Riess03.pdf
Micelle Delivery to Target Cancer Cellshttp://news.uns.purdue.edu/x/2008a/080502ChengCancer.html
Micelles from PEG-PCLMoon Suk Kim, Hoon Hyun, Young Ho Cho, Kwang Su Seo, Woo Young Jang, Sun Kyung Kim, Gilson Khang, Hai Bang Lee. "Preparation of methoxy poly(ethyleneglycol)-blockpoly(caprolactone) via activated monomer mechanism and examination of micellar characterization." Polymer Bulletin 55: p.149-156. 2005.
2. Thermogel/ Tissue engineering
Thermogelling properties of PLA-PEG-PLA triblockhttp://www.pse.umass.edu/gtew/images/Tew-SoftMatter-2005-253.pdf
Thermogelling properties of PEG-PLGA ttp://cobweb.ecn.purdue.edu/~yywon/publications/2000%20Macromolecules%2033(22)%208317-8322%20Thermogeling%20Biodegradable.pdf
“Sol-Gel Transition Temperature of PLGA-g-PEG Aqueous Solutions” Young-Me Chung, Kevin L. Simmons, Anna Gutowska, and Byeongmoon Jeong. Biomacromolecules 2002, 3, 511-516
Thermogelling properties of PEG-Biodegradable"Preparation of Methoxy Poly(ethylene glycol)/Polyester Diblock Copolymers and Examination of the Gel-to-Sol Transition." Moon Suk Kim, Kwang Su Seo, Gilson Kwang, Sun Hang Cho, Hai Bang Lee. Journal of Polymer Science Part A: Polymer Chemistry 42 : p. 5784-5793. 2004.
Thermogelling properties of PLGA-PEG-PLGAhttp://www.tyndall.ie/research/mems/pubs/Pearton%20-%20Gene%20Delivery%20to%20the%20Epidermal%20Cells%20of%20Human%20Skin%20Explants%20Using%20Microfabricated%20Microneedles%20and%20Hydrogel%20Formulations.pdf
Thermogelling properties of PEG-PLA*”Biodegradable Block Copolymers as injectable Drug Delivery Systems” Byeongmoon Jeong, You Han Bae, Doo Sung Lee, and Sung Wan Kim. Nature 388. p. 860-862. 1997.

3.Drug Delivery
Below is an example of solid pellets plasticized to improve the delivery of protein based drugs:“New synthetic absorbable polymers as BMP carriers: Plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers” Naoto Saito, Takao Okada, Shigeyuki Toba, Shimpei Miyamoto, Kunio Takaoka Journal of Biomedical Materials Research Part A Volume 47, Issue 1 , Pages 104 – 110.
4.Benefits
Polyethylene glycol block is known to reduce the adsorption of proteins. From a biocompatibility standpoint, this is an improvement over the relatively hydrophobic PLA/PGA, which may allow protein adsorption. Protein adsorption is the first step towards thrombosis in blood contacting materials. For more information and a comparison study between block and non-block polymer check out:
“Modulation of marrow stromal cell function using poly(D,L-lactic acid)-block-poly(ethylene glycol)-monomethyl ether surfaces” Achim Göpferich, Susan J. Peter, Andrea Lucke, Lichun Lu, Antonios G. Mikos Journal of Biomedical Materials Research Part A Volume 46, Issue 3 , Pages390 – 398.

5.General Degradation Properties
As a general rule, the larger the PEG block relative to the PL/GA the more rapid the degradation.“Degradation behavior of block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments” Maurizio Penco, Silvia Marcioni, Paolo Ferruti, Salvatore D'Antone and Romano Deghenghi. Biomaterials, Volume 17, Issue 16, 1996, Pages 1583-1590

Flamma Fluor Dyes

2009-11-22T20:32:00.001-05:00

Akina, Inc. through a partnership with DKC distributes Flamma Fluorescent dyes. These dyes are ideally suited for applications to biochemistry such as marking proteins/antibodies as well as other fluorescence microscopy applications. Check out: http://www.akinainc.com/flamma-fluor.html for more. Feel free to drop me a line here with questions or comments.

PolyVivo Polymers

2009-11-21T20:55:00.000-05:00

At Akina we make and distribute polymers that we call Polyvivo. These polymers are block combinations of biodegradable polymers (Poly(lactic acid), poly(lactic-co-glycolic) acid, poly(caprolactone) combined with water soluble polyethylene glycol. (check out: http://www.polyvivo.com) If you have questions about these polymers, or would like to discuss them feel free to drop me a line here.