MARCO VIOLA

PhD Graduate

PhD program:: XXXVI


supervisor: Pietro Matricardi

Thesis title: A novel polyacrylate-cholesterol amphiphilic derivative: synthesis, characterization, and investigation as a potential ingredient for topical formulations

Polyacrylic acid (PAA), the synthetic homopolymer of acrylic acid, plays a key role in both pharmaceutical and cosmetic fields for its rheological and mucoadhesive properties. These features may be enhanced and tuned by means of chemical modifications, leading to new derivatives such as block copolymers, cross-linked gels, and amphiphilic polymers. The first two kinds of derivatives were already widely studied, while only a few examples are described in the literature of chemical derivatizations post-polymerization of PAA for the preparation of amphiphilic derivatives. In this study, the synthesis and characterization of an innovative polymer for potential biomedical, cosmetic, and pharmaceutical applications is reported. The novel derivative, “PAAbCH,” is an amphiphilic polyacrylate grafted with cholesterol (CH) moieties on its backbone. Its properties were deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure. The new polymer showed remarkable viscosity-enhancing properties and was able to significantly improve the solubility of poorly water-soluble drug molecules. Furthermore, several water-based pharmaceutical and cosmetic formulations were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process.

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