Tuesday, April 18, 2017

mPEG-PLA from PolySciTech used by Yale University in development of a novel blood-circulation assay method

A fundamental difficulty with medicinal applications to humans is that the circulatory systems of most living organisms are designed specifically to screen out any perceived toxins or ‘non-self’ components. Typically, the kidneys and the liver work together along with macrophages (white blood cells) to remove any chemicals or particulates from the bloodstream. Although this system provides protection to the human body from toxic ingestion, it creates great difficulty for applying medicines as it greatly reduces the blood circulation time of medicinal molecules. For general medicinal applications, the loss of drug from the bloodstream is calculated as the circulation half-life and dosing schedules are calculated to match. One method to improve blood-circulation is to encapsulate the drug molecule inside of PEG-PLA so-called ‘stealth’ nanoparticles. For these particles, the PEG external coating prevents attacks by macrophages while the size alone reduces uptake and clearance by kidneys or liver. These particles enhance the blood circulation time of medicines, but a key question is by exactly how much is the blood circulation time enhanced and what is the new circulation half-life. This question critical for practical applications as it would define the dosing schedule of the encapsulated drug as it must be dosed often enough to maintain effect but not too often so as to potentially have toxic side-effects. Recently, researchers at Yale University utilized mPEG-PLA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AK054) to generate stealth-nanoparticles as test substrates for their novel fluorescence microscopy-based technique for determining half-life of particles using as little as 2 uL of blood. This research holds promise for rapid and routine determination of half-life using very small samples of blood. Read more: Tietjen, Gregory T., Jenna DiRito, Jordan S. Pober, and W. Mark Saltzman. "Quantitative microscopy-based measurements of circulating nanoparticle concentration using microliter blood volumes." Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300643

“Abstract: Nanoparticles (NPs) are potential drug delivery vehicles for treatment of a broad range of diseases. Intravenous (IV) administration, the most common form of delivery, is relatively non-invasive and provides (in theory) access throughout the circulatory system. However, in practice, many IV injected NPs are quickly eliminated by specialized phagocytes in the liver and spleen. Consequently, new materials have been developed with the capacity to significantly extend the circulating half-life of IV administered NPs. Unfortunately, current procedures for measuring circulation half-lives are often expensive, time consuming, and can require large blood volumes that are not compatible with mouse models of disease. Here we describe a simple and reliable procedure for measuring circulation half-life utilizing quantitative microscopy. This method requires only 2 μL of blood and minimal sample preparation, yet provides robust quantitative results. Graphical Abstract: Quantitative microscopy can be used to measure circulating concentrations of nanoparticles with as little as 2 μL of blood. However, when using such small volumes, the path length within and between samples can vary significantly as the high viscosity of blood can yield differences in think layer thickness as the blood spreads following application of a coverslip. This yields variability in the measured mean fluorescence intensity. Addition of a reference nanoparticle of a different color can correct the mean fluorescence intensity variance. Thus, quantitative microscopy can serve as a robust method for measuring nanoparticle half-life using μL volumes of blood. NP formulation: NP were prepared by a standard nanoprecipitation procedure. PLA–PEG (PolyVivo AK054) was dissolved at an initial concentration of 100 mg/mL in DMSO and then diluted to the desired concentration for NP formulation (typically ~55 mg/mL for the ~165 nm NPs used in this study) along with addition of either DiI or DiO dye also dissolved in DMSO. NPs were loaded with DiI or DiO dye at a final wt dye/wt polymer ratio of 0.5%. The dye/polymer solution in DMSO was added drop wise to vigorously stirring sterile diH2O in batches of 200 μL polymer/dye solution added to 1.3 mL of diH2O with identical repetitions performed to generate a full NP batch. NP were subsequently filtered through a 1.2 μm cellulose acetate membrane (GE Healthcare Life Sciences - Whatman) filter to remove any free dye or polymer aggregates and then pooled. Typically, 8 small batches of ~11 mg polymer each were combined for a total pooled batch size of ~88 mg initial polymer weight. The pooled NP solutions were then transferred to a 12 mL volume 10,000 MWCO dialysis cassettes (Thermo Scientific - Slide-A-Lyzer) and dialyzed against 2× exchanges of ~2.2 L of diH2O at room temperature to remove excess DMSO. Following dialysis NPs were aliquoted and snap frozen in liquid N2. One aliquot from each NP batch was lyophilized in a pre-weighed tube in order to determine the NP concentration. Standard NP concentration was typically ~5 mg/mL. NP batches were diluted to ~0.1 mg/mL and analyzed via dynamic light scattering (DLS) to confirm NP size and homogeneity.”


Wednesday, April 12, 2017

PhD Research Thesis from The University of Milan utilizes PLGA from PolySciTech as radical chain transfer agent

Sometimes research holds surprising results. Radical chain transfer is a process which allows for controlling the molecular weight and end-cap properties of poly(vinyl) type polymers. Conventionally, radical chain transfer agents comprise of molecules custom designed for that exact purpose, such as thiol compounds in which the sulfur atom actively participates in the free radical interaction. Conventionally, PLGA is not typically applied to free radical chain transfer however researchers at The University of Milan were able to use PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP059) in this fashion to create PLGA-g-PVP. This research holds promise for the development of novel polymer compounds for a wide array of applications. Read more: Capuano, G. "Amphiphilic, Biodegradable and Biocompatible Polymers for Industrial Applications." (2017). Universita Degli Studi Di Milano Facolta Di Scienze E Tecnologie PhD School in Industrial Chemistry XXIX Cycle PhD Student Capuano Giovanna Thesis. https://air.unimi.it/bitstream/2434/477898/2/phd_unimi_R10587.pdf

 “The aim of this PhD work was to establish the synthetic procedures for new families of biocompatible and biodegradable and/or bioeliminable biomaterials that can be differently processed to obtain nanoparticles, core-shell nanof ibres and hydrogel slabs or conduits, respectively. Depending on composition, size and morphology, these biomaterials may be intended for applications as drug delivery systems and/or tissue regeneration. Specifically, the research project has been developed along two main lines: Synthesis of poly(lactic-glycolic acid)-g-poly(1-vinylpyrrolidin-2-one) (PLGA-g-PVP) copolymers whose architecture consisted of a long PLGA backbone with oligomeric PVP pendants. These were obtained by the radical polymerisation of 1-vinylpyrrolidin-2-one in molten PLGA 50:50, acting as chain transfer agent. Synthesis of a new classes of poly(saccharide)-poly(aminoamine)s 3D-network intended as scaffolds for the regeneration of liver. (Synthesis of PLGA-g-PVP): PLGA (2.012 g, PolyVivo AP059) and VP (0.203 g, 1.83 mol) were added to dichloromethane (30 mL) in a two-necked 100 mL flask equipped with a stir bar. The resultant solution was purged 5 min with nitrogen and AIBN (2.1 mg, 0.013 mmol) was added. Dichloromethane was then eliminated at room temperature and 0.2 tor. After three nitrogen-vacuum cycles, the reaction mixture was heated to 100 °C, maintained at this temperature under nitrogen for 2.5 h, cooled to room temperature and dissolved in dichloromethane (100 mL). The solution was poured drop-wise in diethyl ether (1 L) under vigorous stirring and the resultant slurry stirred for further 2 h. The precipitated product was finally retrieved by filtration, washed with fresh ether (200 mL) and dried under vacuum.” 


Monday, April 10, 2017

Poly(lactide) from PolySciTech used as part of bone-tissue engineering development work in recent patent application

Tissue engineering is an exciting field of research in which a cell scaffold is implanted to heal missing tissue. Normal human cells require a surface to adhere too and grow along. In the human body, this ‘surface’ is a group of cellular excretions, which give biochemical and mechanical (structural) support for the cells, referred to as the ‘extra cellular matrix’ (ECM). Without the ECM, cells cannot grow into the tissue. For this, and other reasons, damaged tissues will sometimes never regrow fully (e.g. amputations, defects, voids, etc.) The goal of tissue engineering is to find a way to replace the extra cellular matrix with a synthetic structure so that the surrounding cells can grow into the void area and replace it with new tissue. Recently, researchers at Pennsylvania State University published a patent in which PLLA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP047) was used as a control for bone-tissue replacement. This material, along with the experimental polymer, was processed into a porous structure by a method known as salt-leaching (see picture, Fig. 4B, for example). The examples of this patent provide excellent data regarding methodologies and use of this polymer in this application. Read more: Yang, Jian. "Methods of Promoting Bone Growth and Healing." U.S. Patent 20170080125, issued March 23, 2017. http://www.freepatentsonline.com/y2017/0080125.html

“Abstract: In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method described herein comprises disposing a graft or scaffold in a bone growth site. The graft or scaffold comprises (a) a polymer network formed from the reaction product of (i) citric acid, a citrate or an ester of citric acid with (ii) a polyol. The graft or scaffold further comprises (b) a particulate inorganic material dispersed in the polymer network.”

Friday, March 31, 2017

PLGA from PolySciTech used for development of NIR fluorescent dye delivery carrier to make tumors detectable through skin as a diagnostic aid

Near-infrared (NIR) is a frequency of light just outside of the range of human vision which can be seen through human flesh. The delivery of NIR fluorophores to cancer cells and other diseased tissues can provide for the opportunity to render cancer detectable through the skin by NIR fluorescent techniques. Recently, researchers at Wroclaw University (Poland) used PLGA from PolySciTech (PolyVivo AP062) to stabilize NIR active NaYF4:Er3+,Yb3 nanoparticles in a double emulsion along with nonionic surfactants. This research holds promise for allowing for improved cancer diagnostics by making tumors visible through the skin. Read more: Bazylińska, Urszula, and Dominika Wawrzyńczyk. "Encapsulation of TOPO stabilized NaYF 4: Er 3+, Yb 3+ nanoparticles in biocompatible nanocarriers: synthesis, optical properties and colloidal stability." Colloids and Surfaces A: Physicochemical and Engineering Aspects (2017). http://www.sciencedirect.com/science/article/pii/S092777571730300X


“Abstract: The emulsification process leading to up-converting NaYF4:Er3+,Yb3+ NPs encapsulation, was performed using a modified water/oil/water double emulsion evaporation method, where poly(lactic-co-glycolic acid) was used as biocompatible polymer. Span 80 and Cremophor A25 were applied as non-ionic surfactants and dichloromethane as oily phase. The use of trioctylphosphine oxide ligands for the synthesis of up-converting NaYF4:Er3+,Yb3+ NPs allowed to obtain spherical particles with sizes below 10 nm, what further facilitated the efficient encapsulation process. Those newly designed nanosystems were subjected to analysis of their morphology, colloidal stability and optical properties by: dynamic light scattering, ζ-potential, atomic force microscopy, transmission electron microscopy and measuring the up-conversion emission spectra of free and loaded NaYF4:Er3+,Yb3+ NPs. The encapsulated NaYF4:Er3+,Yb3+ NPs showed increased colloidal stability for a long period of 60 days of storage in different conditions. Simultaneously, the encapsulation process did not significantly influenced their optical properties and strong visible emission could be observed upon nearinfrared excitation. Highlights: NaYF4:Er,Yb NPs 5 nm in size were synthesized with TOPO used as a stabilizing ligands. The modified double emulsion evaporation method was successful in the up-converting NPs encapsulation. PLGA, Span 80 and Cremophor A25 act as the obtained nanosystems stabilizers. The encapsulation process retain the optical properties of NaYF4:Er3+,Yb3+ NPs. The obtained nanocarriers have potential applications as theranostic agents.”

Tuesday, March 28, 2017

mPEG-PCL from PolySciTech utilized in development of Chrysin-nanoparticle based therapy for lung-cancer


Lung cancer is among the leading causes of cancer-related death worldwide. Chrysin, a natural active flavone, acts to enhance the chemotherapeutic effectiveness of other chemoagents (cisplatin, docetaxel, etc.) against lung cancer. Chrysin’s usability, however, is limited by its very poor water solubility and low bioavailability. Recently, researchers at Duksung Women’s University (Korea) utilized mPEG-PCL from PolySciTech (www.polyscitech.com) (PolyVivo #: AK001) to formulate chrysin-loaded nanoparticles which were found to delay tumor progression in a mouse model. This research holds promised for improved lung-cancer therapy. Read more: Kim, Kyoung Mee, Hyun Kyung Lim, Sang Hee Shim, and Joohee Jung. "Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles." International Journal of Nanomedicine 12 (2017): 1917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352247/


“Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model. Nanoparticle preparation method: Chrysin (Sigma-Aldrich, St Louis, MO, USA) was incorporated into copolymer NPs using an oil-in-water technique (Figure 1). mPEG–β-polycaprolactone copolymer (mPEG-PCL, 50 mg; 2,000:5,200 Da; PolySciTech, West Lafayette, IN, USA) and 5 mg of chrysin were dissolved in a dichloromethane (Duksan reagent, Gyeonggi-do, Korea) and methanol mixture (Duksan reagent; v/v, 1.5:1). This solution (2.5 mL) was added to a 1% aqueous polyvinyl alcohol solution (6 mL) and was emulsified by sonification for 1 min. The solvent was removed by evaporation under stirring to produce NPs. To remove polyvinyl alcohol and surplus free chrysin, the supernatant was collected after centrifugation (14,000 rpm) twice at room temperature for 1 h.”

Monday, March 27, 2017

T-shirt

PolySciTech: Keeping scientists and engineers fashionably dressed since 2013.  (www.polyscitech.com, free t-shirt with select orders)


Wednesday, March 22, 2017

PLGA from PolySciTech used in optimizing 3D printing techniques for tissue engineering

A relatively recent and powerful tool for both manufacturing and research has been developed in 3D printing. Despite it’s advantages, 3D printing is restricted based on the polymeric material’s melt and processing properties. Recently, researchers working jointly at University of Maryland, Cornell University, and Rice University screened through a series of PLGA materials in order to define the optimal printing procedures for each. The utilized a series of PLGA’s from PolySciTech (www.polyscitech.com) (PolyVivo AP039, AP137, AP076, and AP024) and optimized their printing configurations for bone-tissue engineering. This research holds promise for the capability to print biocompatible, biodegradable parts for tissue engineering and other applications. Read more at: Guo, Ting, Timothy Holzberg, Casey Lim, Feng Gao, Ankit Gargava, Jordan Trachtenberg, Antonios Mikos, and John Fisher. "3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution." Biofabrication (2017). http://iopscience.iop.org/article/10.1088/1758-5090/aa6370/meta

“Abstract: In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meets patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography (microCT) was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.”