Friday, May 26, 2017

PolySciTech polyesters used in development of neuroprotective controlled-delivery system for glaucoma treatment

Glaucoma, a disease in which damage to the optic nerve leads to eventual blindness, involves oxidative stress that leads to extensive optic nerve injury. Preventing oxidative stress (e.g. reducing reactive oxygen species formation with the cells) is an effective means to prevent cellular death and delay nerve damage. It has been found that reducing agents (such as phenylphosphine-borane complexes) can act to prevent the over-formation of reactive oxygen species and reduce nerve damage from Glaucoma. Administering these medicines over the course of this chronic disease, however, requires repeat injections in the same ocular location, which is inconvenient to both patient and provider. A better strategy is to deliver a single injection every few months which delivers the neuroprotective agent in a controlled manner. Recently, researchers working at University of Wisconsin and McGill University (Canada) utilized many degradable polyesters (PLGA, PLA, PLCL, PDOCL) from PolySciTech ( (PolyVivo cat# AP001, AP002, AP003, AP004, AP006, AP007, AP008, AP010, AP011, AP013, AP014, AP016, AP017, AP018, AP020, AP021, AP023, AP024, AP030, AP031, AP032, and AP034) to develop such a controlled delivery system. This research holds promise for improved glaucoma therapy to delay the progression of this disease. Read more: Janus, David A., Christopher J. Lieven, Megan E. Crowe, and Leonard A. Levin. "Polyester-Based Microdisc Systems for Sustained Release of Neuroprotective Phosphine-Borane Complexes." Pharmaceutical Development and Technology just-accepted (2017): 1-32.

“Abstract: Phosphine-borane complexes are recently developed redox-active drugs that are neuroprotective in models of optic nerve injury and radioprotective in endothelial cells. However, a single dose of these compounds is short-lived, necessitating development of sustained-release formulations of these novel molecules. We screened a library of biodegradable co- and non-block polyester polymer systems for release of incorporated phosphine-borane complexes to evaluate them as drug delivery systems for use in chronic disease. Bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) was combined with biodegradable polymers based on poly(D,L-lactide) (PDLLA), poly(L-lactide) (PLLA), poly(caprolactone) (PCL), poly(lactide-co-glycide) (PLGA), or poly(dioxanone-co-caprolactone) (PDOCL) to make polymer microdiscs, and release over time quantified. Of 22 polymer-PB1 formulations tested, 17 formed rigid polymers. Rates of release differed significantly based on the chemical structure of the polymer. PB1 released from PLGA microdiscs released most slowly, with the most linear release in polymers of 60:40 LA:GA, acid endcap, Mn 15,000-25,000 and 75:25 LA:GA, acid endcap, Mn 45,000-55,000. Biodegradable polymer systems can therefore be used to produce sustained-release formulations for redox-active phosphine-borane complexes, with PLGA-based systems most suitable for very slow release. Sustained release could enable translation to a clinical neuroprotective strategy for chronic diseases such as glaucoma. Keywords: Phosphine-Borane, Sustained Release, Polymer, Polyester, Neuroprotection”
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