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Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries

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Polyester-based microdisc systems for sustained release of neuroprotective phosphine-borane complexes.

David A Janus¹, Christopher J Lieven¹, Megan E Crowe¹

¹a Department of Ophthalmology and Visual Sciences , University of Wisconsin School of Medicine and Public Health , Madison , WI , USA.

Pharmaceutical Development and Technology

|May 20, 2017

Summary

Sustained-release formulations of phosphine-borane complexes were developed using biodegradable polymers. Poly(lactide-co-glycolide) (PLGA) microdiscs demonstrated the slowest and most linear release, ideal for chronic disease drug delivery.

Keywords:

Phosphine-borane neuroprotection polyester polymer sustained release

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Area of Science:

Biomaterials Science
Drug Delivery Systems
Neuropharmacology

Background:

Phosphine-borane complexes are novel redox-active drugs with demonstrated neuroprotective and radioprotective effects.
The short duration of action of a single dose necessitates the development of sustained-release formulations.
Biodegradable polymers offer a promising platform for controlled drug delivery.

Purpose of the Study:

To evaluate biodegradable polyester polymer systems for sustained release of phosphine-borane complexes.
To identify optimal polymer formulations for long-term delivery of these novel therapeutic agents.
To assess the potential of these formulations for treating chronic neurodegenerative diseases.

Main Methods:

Screening of various biodegradable co- and non-block polyester polymers including PDLLA, PLLA, PCL, PLGA, and PDOCL.
Incorporation of bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) into polymer microdiscs.
Quantification of PB1 release rates over time for 22 different polymer-PB1 formulations.

Main Results:

Seventeen out of 22 tested polymer-PB1 formulations resulted in rigid polymers.
Significant differences in drug release rates were observed based on polymer chemical structure.
Poly(lactide-co-glycolide) (PLGA) microdiscs exhibited the slowest and most linear release profiles, particularly specific formulations with defined LA:GA ratios and molecular weights.

Conclusions:

Biodegradable polymer systems are effective for creating sustained-release formulations of redox-active phosphine-borane complexes.
PLGA-based systems are particularly suitable for achieving very slow and controlled release.
Sustained release of these complexes holds potential for clinical translation as a neuroprotective strategy for chronic conditions like glaucoma.