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)-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 composed 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 of around 2-3 wt % and was fully characterized by size exclusion chromatography, NMR, and diffusion ordered NMR spectroscopy. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression molding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (differential scanning calorimetry), thermal stability (thermogravimetry analysis), 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 toward 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 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.

Droplet Fusion in Oil-in-Water Pickering Emulsions.

We have formed compound droplets made of two or more drops of immiscible oils by temporarily destabilizing Pickering oil-in-water emulsions. The emulsions used are synergistically stabilized by mixtures of cationic surfactant and negatively-charged particles. They are highly sensitive to the concentration of surfactant present in the emulsions. We took advantage of transient droplet coalescence events that are triggered by reducing the surfactant concentration to fuse together drops of immiscible oils. This study provides guidelines for designing compound droplets by transient (or limited) coalescence in Pickering emulsions. We show that the possible geometries of particle-stabilized compound drops are determined by the interfacial tensions and relative volumes of the drops fused together. The implications of our results for designing strategies to fabricate multiphase drops are discussed.