Polyester-polydopamine copolymers for intravitreal drug delivery: role of polydopamine drug-binding properties on extending drug release

ABSTRACT

This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-graft-poly(dopamine) (PCL-g-PDA) has been synthesized, and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants made of poly(lactide) and poly(lactide-co-glycolide). The innovative biomaterial combines the documented drug-binding properties of melanin naturally present in the eye, with the established ocular tolerability and biodegradation of polyester implants. The PCL-g-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content around 2-3 wt.%, and was fully characterised by SEC, NMR, and DOSY NMR. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression moulding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (DSC), thermal stability (TGA), degradability and in vitro cytotoxicity. PCL and PCL-g-PDA implants exhibited similar degradation properties in vitro and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic towards L929 and ARPE-19 cells. The drug-loading and in vitro release properties of the new materials were investigated with dexamethasone (DEX) and ciprofloxacin hydrochloride (CIP) as representative drugs featuring low and high melanin binding affinities, respectively. In comparison to unmodified PCL, PCL-g-PDA implants showed significant extension of drug release most likely because of specific drug-catechol interaction with the PDA moieties of the copolymer. The present study confirms the advantages of designing PDA-containing polyesters as a class of biodegradable and biocompatible thermoplastics that can modulate and remarkably extend drug release kinetics thanks to their unique drug binding properties, especially, but not limited to, for ocular applications.