Drug-Eluting Biodegradable Implants for the Sustained Release of Phosphonates

Overview

Journal Polymers (Basel)

Publisher MDPI

Date 2020 Dec 10

PMID 33297466

Citations 6

Authors

Cintya Dharmayanti

Todd A Gillam

Desmond B Williams

Anton Blencowe

Affiliations

Soon will be listed here.

Abstract

Despite being one of the first-line treatments for osteoporosis, the phosphonate drug class exhibits an extremely low oral bioavailability (<1%) due to poor absorption from the gastrointestinal tract. To overcome this, and to explore the potential for sustained drug release, bioerodible poly(lactic acid) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) implants loaded with the phosphonate alendronate sodium (ALN) were prepared via hot-melt extrusion. The rate of drug release in vitro was modulated by tailoring the ratio of lactide to glycolide in the polymer and by altering the ALN-loading of the implants. All investigated implants exhibited sustained ALN release in vitro between 25 to 130 days, where implants of greater glycolide composition and higher ALN-loadings released ALN more rapidly. All PLGA implants demonstrated a sigmoidal release profile, characterised by an initial surface dissolution phase, followed by a period of zero-order drug diffusion, then relaxation or erosion of the polymer chains that caused accelerated release over the subsequent days. Contrastingly, the PLA implants demonstrated a logarithmic release profile, characterised by a gradual decrease in ALN release over time.

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