Injectable biodegradable microchamber array films for long-term delivery of glucocorticoids

Abstract

Glucocorticoids (GCs) are widely recognized for their potent anti-inflammatory and analgesic effects. Although they can cause an array of side effects when delivered systemically these are generally avoided when delivered locally at disease sites such as the eyes, lungs and joints. Glucocorticoid formulations for local use range from crystals and particles through to non-biodegradable implants. In many formulations burst release means that their effectiveness does not persist for more than a few weeks. Novel delivery methods that achieve prolonged delivery of GCs along with sequential degradation of the polymer vehicle has the potential to enhance the effectiveness of these drugs and achieve better control of disease. In this study we use a soft lithography method to produce polymer microchamber array films (MCAs) containing crystals of GCs. We demonstrate that the rate of glucocorticoid release can be adjusted through the choice of polymer used in the manufacture of films with rapid release observed with PLGA 50/50 over the course of 9 weeks and the longest duration of release observed with PLA films which continued beyond a year. Importantly, these release studies do not show evidence of burst release and all films displayed a significant duration of zero order release kinetics. Observations of film degradation were made through changes in their size, microscopic appearance and liberation of lactic acid from the films during the course of experiments demonstrated the association with GC release kinetics. These flexible films can be rolled into fibers with little change in release kinetics and the rolled MCAs can also be injected in vivo through a syringe needle to a delivery site. We envisage that this study could lead to an innovative approach to achieve prolonged release of GCs from biodegradable formulations at disease sites.