Monday, December 7, 2009

PolyVivo FAQ

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.dochttp://www.personal.psu.edu/faculty/r/x/rxn/1989-J%20Chem%20Phys-90-p1980-1994.pdfhttp://www.personal.psu.edu/faculty/r/x/rxn/1989-J%20Chem%20Phys-90-p1980-1994.pdfhttp://www.personal.psu.edu/faculty/r/x/rxn/1993-Langmuir-9-p369-375.pdfhttp://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
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