Mathematical modelling of antibacterial release from a biphasic gel system

Bacterial infections represent an important problem in the orthopaedic field as they can develop either immediately after the surgical intervention or after some years [1]. In particular, they can be very problematic in the case of implants as, often, their elimination requires the surgical removal of the infected implant. Accordingly, a possible solution strategy is to act locally by coating the implant by an antibacterial system that has to be easily applicable, biocompatible (it must not hinder implant osseointegration) and able to provide the desired release kinetics of the selected antibacterial drug. In this frame, this paper focuses the attention on a biphasic polymeric system made up by a thermos-reversible hydrogel, constituted by Poloxamer 407, hosting a dispersed phase represented by polylactic-co-glycolic acid 50:50 (PLGA) micro-particles containing the antibacterial drug (vancomycin hydrochloride). While below room temperature, the Poloxamer 407/water system behaves as a solution and it is easily spreadable on the implant surface, upon temperature rise to the physiological value, the Poloxamer 407/water solution undergoes gelation. Basically, gelation ensures that the PLGA micro-particles remain in situ, between the implant surface and the growing bone. On the contrary, the controlled drug delivery is due to vancomycin hydrochloride release from PLGA micro-particles, acting as the reservoir phase. The primary aim of this paper is to develop a mathematical model able to properly describe the in vitro vancomycin hydrochloride release from the biphasic system.