The Synthesis of High Molecular Weight Partially Hydrolysed Poly(vinyl alcohol) Grades Suitable for Nanoparticle Fabrication

Abstract

Poly(vinyl alcohol) (PVA) is a highly versatile synthetic polymer that is formed by full or partial hydrolysis of poly(vinyl acetate) (PVAc). A wide range of PVA partially hydrolysed grades are commercially available, but the amphiphilic grades of the polymer (30–60% hydrolysis), which probably the most interesting in terms of drug delivery, are not readily available. As a consequence few studies have assessed the application of low hydrolysis PVA polymers to form nanocarriers. The aims of this study were to synthesise amphiphilic grades of PVA on a laboratory scale, analyse their chemical properties and determine whether these grades could be used to form nanoparticles. PVA 30%, PVA 40%, PVA 50% and PVA 60% were synthesised via direct saponification of PVAc. All grades of PVA synthesised had degrees of hydrolysis close to those predicted from the stoichiometry of the saponification reaction. The PVA grades displayed <1.5% batch to batch variability (n = 3) in terms of percentage hydrolysis, demonstrating the manufacture process was both reproducible and predictable. Analysis of the polymer characteristics using 13C nuclear magnetic resonance and differential scanning calorimetry revealed that all PVA grades contained block distributions (i.e., η < 1) of vinyl alcohol monomers (η ranged from 0.33–0.45) with a high probability of adjacency calculated for the hydroxylated units (POH ranged 0.926–0.931). All the grades of PVA formed nanoparticles using a precipitation technique with a trend towards smaller particle size with increasing degree of PVA hydrolysis; PVA 30% resulted in significantly larger nanoparticles (225 nm) compared to PVA 40–60% (137–174 nm).