3D printing of drug-loaded multi-shell rods for local delivery of bevacizumab and dexamethasone: A synergetic therapy for retinal vascular diseases

Abstract

The clinical therapy for retinal vascular diseases requires repeated intravitreal injections of drugs owing to their short half-life, which imposes health and economic burdens on patients. Therefore, it is necessary to develop an advanced drug delivery system that can prolong the drug activity and minimize secondary complications. In this study, we developed a core/shell drug-loaded rod (drug rod) to deliver two types of drugs (bevacizumab (BEV) and dexamethasone (DEX)) from a single implant. The coaxial printing technique allowed BEV and DEX to be released with different kinetics at the same site by using a polymeric shell and a hydrogel core, respectively. The suggested printing technique facilitates the production of drug rods with various dimensions and drug concentrations, and the multi-layered design allows to adjust the release profile of dual drug-delivery system. The rod was injected in rat vitreous less invasively using a small-gauge needle. Further, we validated the efficacy of the implanted drug rods in inhibiting inflammatory responses and long-term suppression of neovascularization compared to the conventional intravitreal injection of BEV in animal model, indicating that the drug rods can be an alternative therapeutic approach for the treatment of various types of retinal vascular diseases.

Keywords: Anti-angiogenesis; Co-axial printing; Multiple drug delivery; Retinal vascular disease; Time-controlled release.