Evaluating the in vivo stability of water-soluble PEG-PLA copolymers using FRET imaging

March 25, 2023

Abstract

Biodegradable and biocompatible polymer materials with tunable physical properties present a great interest for controlled drug delivery applications. A good example is BEPO®, a clinical-stage in situ-forming depot technology based on the utilization of a blend of poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) diblock and triblock amphiphilic copolymers dissolved in an organic solvent. Once injected, this technology will form a bioresorbable solid polymer depot that will allow the release of a drug from weeks to months. The safety of the final degradation products from this technology, i.e., PEG and lactic acid, is well-documented. However, little information exists about the fate of intermediate degradants, specifically of water-soluble PEG-PLA chains where the molecular weights of the PLA block are short. Herein, we designed a Förster Resonance Energy Transfer (FRET) system for short copolymers, suitable for longitudinal in vivo imaging in the subcutaneous space, allowing to follow the stability of these products. Our results confirm that these species, that might be leaked from BEPO® depots during degradation, are rapidly hydrolyzed in the subcutaneous space of mice, forming approved products by Health Authorities, i.e., PEG and PLA homopolymers and/or lactic acid.

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