Polyester-Polydopamine Copolymers for Intravitreal Drug Delivery: Role of Polydopamine Drug-Binding Properties in Extending Drug Release.

This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in a sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-<i>graft</i>-poly(dopamine) (PCL-<i>g</i>-PDA) has been synthesized and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants composed of poly(lactide) and poly(lactide-<i>co</i>-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-<i>g</i>-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content of around 2-3 wt % and was fully characterized by size exclusion chromatography, NMR, and diffusion ordered NMR spectroscopy. The thermoplastic nature of PCL-<i>g</i>-PDA allowed its simple processing by hot-melt compression molding to prepare small implants. The properties of unmodified PCL and PCL-<i>g</i>-PDA implants were studied and compared in terms of thermal properties (differential scanning calorimetry), thermal stability (thermogravimetry analysis), degradability, and <i>in vitro</i> cytotoxicity. PCL and PCL-<i>g</i>-PDA implants exhibited similar degradation properties <i>in vitro</i> and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic toward L929 and ARPE-19 cells. The drug loading and <i>in vitro</i> 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-<i>g</i>-PDA implants showed a 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 the drug release kinetics thanks to their unique drug-binding properties, especially, but not limited to, for ocular applications.