Investigating the potential of degradable poly(vinyl acetate) copolymer microparticles for encapsulation and in vitro release studies

Abstract

Poly(vinyl acetate) is a well-known polymer synthesized through the free radical polymerization of vinyl acetate (VAc) monomer. However, enhancing the degradability of this polymer is best achieved by copolymerizing cyclic ketene acetal (CKA) with VAc. Despite their potential, the practical use of these degradable polymers remains limited. Therefore, our study aimed to develop a sustainable technology encompassing the synthesis and application of poly(VAc-co-MDO), and environmental biodegradability of poly(vinyl alcohol (VA)). To achieve this, we synthesized a series of degradable copolymers, namely poly(VAc-co-MDO), via free radical ring-opening polymerization (rROP) of 2-methylene-1,3-dioxepane (MDO) with VAc. The number of degradable ester units in the polymer backbone was systematically controlled by varying the initial monomer feed compositions, resulting in a range of 8–85 mol%. To compare their properties, we also synthesized homopolymers, namely poly(VAc) and poly(MDO). Subsequently, we formulated the homo and copolymers into microparticles using the co-solvent evaporation method, which yielded spherical particles with a particle size distribution ranging from 5 to 10 µm. Furthermore, we demonstrated the applicability of these degradable copolymers, exemplified by a poly[VAc(0.92)-co-MDO(0.08)] with 8 mol% MDO in the polymer backbone, in an encapsulation modeling study using curcumin as the active molecule. Successful encapsulation of curcumin into degradable polymer particles was confirmed and quantified via HPLC analysis. The degradability of the copolymers was evaluated through accelerated alkali hydrolysis, resulting in the formation of oligomeric degradation products. Additionally, we investigated the environmental biodegradability of poly(VA-co-MDO) as a proof of concept, revealing a biodegradability of 89% within 28 days for this polymer consisting of 88 mol% poly(VA) and 12 mol% poly(MDO) in the backbone. Preparing stable formulation for applications and performing biodegradability tests for the copolymers or microparticles derived from random poly(VAc-co-MDO) was challenging due to the insolubility of the polymer or instability in the form of sedimentation of the microparticles in the inoculum. Hence, in order to achieve stable formulation, we synthesized random poly(VA-co-MDO) through the selective cleavage of chloroacetyl group (ClAc) from its precursor, poly(VClAc-co-MDO). This method was preferred because obtaining poly(VA-co-MDO) directly from poly(VAc-co-MDO) was hindered by significant ester backbone cleavage, even under mild conditions. Our research assumes significance in light of recent restrictions imposed by various chemical agencies on the use of non-degradable polymers and microparticles in formulations.