Abstract
The ocular diseases are a major public health issue. More than 216 million people are visually impaired and another 36 million people are estimated to be blind worldwide. Currently, research is focusing on formulations providing sustained delivery of active pharmaceutical ingredient (APIs) using intravitreal administration for the treatment of retinal pathologies. At present, only one biodegradable implant loaded with small API is commercially available (Ozurdex™), and no commercial polymeric formulation is found for the delivery of large API. Consequently, this project focuses on the development of new solid implants or in-situ gelling formulations based on poly(ethylene glycol) (PEG) and/or poly(ε-caprolactone) (PCL) (approved by the Food and Drug Administration) functionalized with poly(dopamine) (PDA) (already used in cancer treatment) by exploiting PDA-API interactions. The PCL and PCL-g-PDA implants are obtained by hot compression. The in vitro studies show the degradability and the non-cytotoxicity (L929 and ARP19 cells lines) of the implants. To modulate the release kinetics, the PCL and PCL-g-PDA proportion and the nature of the small molecule are adjusted. The PCL-g-PDA implants allow the release over 5 months without lag time. The liquid formulations based on PCL-b-PEG-b-PCL and/or (PCL-g-PDA)-b-PEG-b-(PCL-g-PDA) are formulated in small molecular weight PEG and water to enhance the solubility of the components. They allow injectability through small 30G needle and stability of the antibody. The in vitro release studies show the release of the antibody within 3 days. The two strategies open perspectives for the development of innovative ocular drug delivery copolymer systems.