Monthly Archives: November 2015

PLGA and PEG-PLGA investigated for release of neuregulin as part of heart-attack treatment

PolySciTech Division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA and block PEG-PLGA copolymers. Recently, these polymers have been used for development of microparticles which deliver the neuregulin growth factor into damaged heart tissue. It was found that the MPs were able to reside in the cardiac tissue and release active neuregulin for up to three months and that PEGylated PLGA resisted phagocytosis. Read more: Pascual-Gil, S., T. Simón-Yarza, E. Garbayo, F. Prosper, and M. J. Blanco-Prieto. “Tracking the In vivo release of bioactive NRG from PLGA and PEG-PLGA microparticles in infarcted hearts.” Journal of Controlled Release (2015). http://www.sciencedirect.com/science/article/pii/S0168365915302236

 

“Abstract: The growth factor neuregulin (NRG) is one of the most promising candidates in protein therapy as potential treatment for myocardial infarction (MI). In the last few years, biomaterial based delivery systems, such as polymeric microparticles (MPs) made of poly(lactic co glycolic acid) and polyethylene glycol (PLGA and PEG–PLGA MPs), have improved the efficacy of protein therapy in preclinical studies. However, no cardiac treatment based on MPs has yet been commercialized since this is a relatively new field and total characterization of polymeric MPs remains mandatory before they reach the clinical arena. Therefore, the objective of this study was to characterize the in vivo release, bioactivity and biodegradation of PLGA and PEG–PLGA MPs loaded with biotinylated NRG in a rat model of MI. The effect of PEGylation in the clearance of the particles from the cardiac tissue was also evaluated. Interestingly, MPs were detected in the cardiac tissue for up to 12 weeks after administration. In vivo release analysis showed that bNRG was released in a controlled manner throughout the twelve week study. Moreover, the biological cardiomyocyte receptor (ErbB4) for NRG was detected in its activated form only in those animals treated with bNRG loaded MPs. On the other hand, the PEGylation strategy was effective in diminishing phagocytosis of these MPs compared to noncoated MPs in the long term (12 weeks after injection). Taking all this together, we report new evidence in favor of the use of polymeric PLGA and PEG–PLGA MPs as delivery systems for treating MI, which could be soon included in clinical trials. Keywords: Myocardial infarction; Microparticles; Protein therapy; Phagocytosis; Bioactivity; Biotinylation”

Image: http://4.bp.blogspot.com/-SHNzltHYoz0/VlM8WUcwLkI/AAAAAAAAB8Q/mlEXRNakaCY/s1600/Pascual-Gil%252C%2B2015%2BPLGA%2Bneuregulin%2Bheart-attack%2Btreatment.png

PCL-PEG block copolymers investigated for joint repair

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers for a variety of applications including PCL-PEG block copolymers. Recently PEG-PCL block copolymers were investigated in regards to use as a lubricating surface for artificial knee joints and tested for their ability to withstand simulated ‘walking’ conditions. Read more: Hsu, Chih Yueh, Chin Chung Wei, and Cho Pei Jiang. “Tribological Study of PCL-PEG-PCL Polymer on SiNxHy Base.” In Key Engineering Materials, vol. 642, pp. 264-269. 2015. http://www.scientific.net/KEM.642.264

“Abstract: Tribological behaviour of polymer and hard coating films is complicated with bio-lubricant. Contacting and kinematic conditions of a knee joint when a person in running was simulated in the study. Substrates of specimens are Ti6Al4V and 316LVM stainless steel. Two kinds of polymer films, PCL-PEG-PCL and mPEG-PCL-mPEG, were used to simulate the tissue of cartilage. The silicon nitride film, SiNxHy prepared by PECVD, was used as a protecting film, and it’s thickness about 1000 nm under the polymer film. The testing device was developed, upper specimen is rotated reversely and the lower one is moved linearly forward and backward for 6 mm. A frequency vibration is applied under the lower specimen to simulate the vibration caused from walking, which is sated 2 Hz. Two torque meters are used for friction measurement in rotational and sliding directions. Experiments simulated vertical vibration, rotary and reciprocating motion. Comparing friction coefficient with different substrates with SiNxHy film, mixture of PCL-PEG-PCL and bovine serum can effectively decrease friction but useless for mPEG-PCL-mPEG. If adhesion of PCL-PEG-PCL polymer can be improved, it has potential in the application of artificial joint. Keywords: Friction, Pin on Disc, Polymer, Vertical Vibration”

PLGA-PEG-Maleimide used for development of improved ocular delivery system

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide variety of active end-capped PLGA-PEG precursors for development of targeted nanoparticles. Recently, PLGA-PEG-Maleimide was used to generate peptide conjugated nanoparticles for improved ocular delivery. Read more: Vasconcelos, Aimee, Estefania Vega, Yolanda Pérez, María J. Gómara, María Luisa García, and Isabel Haro. “Conjugation of cell-penetrating peptides with poly (lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery.” International journal of nanomedicine 10 (2015): 609. Full-text http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315550/

“Abstract: In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. Keywords: peptide for ocular delivery, flurbiprofen, controlled release, ocular tolerance, anti-inflammatory”

mPEG-PCL used for genistein delivery micelle formation

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides many block polymers including methoxy-poly(ethylene glycol)-poly(caprolactone) (mPEG-PCL). The methoxy serves as an inert blocking endcap, the PEG chain serves as a hydrophilic, water-soluble polymer to stabilize particles in aqeous solution and the PCL chain serves as a hydrophobic portion that can interact with poorly-water soluble drugs. Because of these properties, under the right conditions, this kind of polymer can self-assemble into micelles or nanoparticles which have a hydrophobic core for carrying medicinal molecules and hydrophilic PEG layer on the exterior to stabilize the particles in aqueous solutions. Recently, this kind of polymer was used by researchers at Jinan University to generate nano-carriers containing genistein, a poorly-soluble isoflavone that performs as a potent antitumor medicine, to improve the deliverability of this molecule. PolySciTech has recently launched a new mPEG-PCL product, AK105 (mPEG-PCL 5000-8000Da), which can be used for similar applications. Read more: Zhang, Tianpeng, Huan Wang, Yanghuan Ye, Xingwang Zhang, and Baojian Wu. “Micellar emulsions composed of mPEG-PCL/MCT as novel nano-carriers for systemic delivery of genistein: a comparative study with micelles.” International journal of nanomedicine 10 (2015): 6175. Full-Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598212/

“Abstract: Polymeric micelles receive considerable attention as drug delivery vehicles, depending on the versatility in drug solubilization and targeting therapy. However, their use invariably suffers with poor stability both in in vitro and in vivo conditions. Here, we aimed to develop a novel nanocarrier (micellar emulsions, MEs) for a systemic delivery of genistein (Gen), a poorly soluble anticancer agent. Gen-loaded MEs (Gen-MEs) were prepared from methoxy poly(ethylene glycol)-block-(ε-caprolactone) and medium-chain triglycerides (MCT) by solvent-diffusion technique. Nanocarriers were characterized by dynamic light scattering, transmission electron microscopy, and in vitro release. The resulting Gen-MEs were approximately 46 nm in particle size with a narrow distribution. Gen-MEs produced a different in vitro release profile from the counterpart of Gen-ME. The incorporation of MCT significantly enhanced the stability of nanoparticles against dilution with simulated body fluid. Pharmacokinetic study revealed that MEs could notably extend the mean retention time of Gen, 1.57- and 7.38-fold as long as that of micelles and solution formulation, respectively, following intravenous injection. Furthermore, MEs markedly increased the elimination half-life (t1/2β) of Gen, which was 2.63-fold larger than that of Gen solution. Interestingly, Gen distribution in the liver and kidney for MEs group was significantly low relative to the micelle group in the first 2 hours, indicating less perfusion in such two tissues, which well accorded with the elongated mean retention time. Our findings suggested that MEs may be promising carriers as an alternative of micelles to systemically deliver poorly soluble drugs. Keywords: genistein, micellar emulsions, stability, pharmacokinetics, tissue distribution”

Fluorescently conjugated chitosan from Akina, Inc used for microcapsule formation

PolySciTech division of Akina, Inc. provides a variety of modified chitosan products (https://akinainc.com/polyscitech/products/Kitopure/index.php) as well as other polymers and research products. Chitosan has a net positive charge due to amine units along the chain. When chitosan interacts with a negatively charged polymer the two bind together due to ionic attraction between the polymer chains forming what is called a polyelectrolyte complex. Recently, researchers at Yale University and the Université Paris Diderot, used fluorescently conjugated chitosan (a cationic polymer) from Akina, Inc. along with sulfonated styrene (an anionic polymer) to generate microcapsules held together by the polyelectrolyte complex formed between these two polymers. Read more: Kaufman, Gilad, Rostislav Boltyanskiy, Siamak Nejati, Abdou R. Thiam, Michael Loewenberg, Eric R. Dufresne, and Chinedum O. Osuji. “Single-step microfluidic fabrication of soft monodisperse polyelectrolyte microcapsules by interfacial complexation.” Lab Chip 14, no. 18 (2014): 3494-3497. http://pubs.rsc.org/en/content/articlepdf/2014/lc/c4lc00482e Full-Text: http://www.researchgate.net/profile/Siamak_Nejati/publication/263933420_Single-step_microfluidic_fabrication_of_soft_monodisperse_polyelectrolyte_microcapsules_by_interfacial_complexation/links/5419c56c0cf2218008bf9faa.pdf

“Abstract: Common methods for fabrication of polyelectrolyte microcapsules rely on a multi-step process. We propose a single-step approach to generate polyelectrolyte microcapsules with 1–2 μm shells based on polyelectrolyte complexation across a water/oil droplet interface and study the effect of parameters controlling the polyelectrolyte complexation on shell thickness.”

Image: http://3.bp.blogspot.com/-HRj6EdCatac/Vjzww3jWNtI/AAAAAAAAB7I/mHKXxylN09E/s1600/Kaufman%252C%2B2014%2Bmicrocapsules.png