Effect of the Subcutaneous Environment on Phase-Sensitive In Situ-Forming Implant Drug Release, Degradation, and Microstructure

In situ-forming implants are a promising platform used for the release of therapeutic agents. Significant changes in behavior occur when the implants are used in vivo relative to implants formed in vitro. To understand how the injection site effects implant behavior, poly(lactic-co-glycolic acid) implants were examined after injection in the subcutaneous space of a Sprague-Dawley rat model to determine how the environment altered implant erosion, degradation, swelling, microstructure, and mock drug release. Changes in implant microstructure occurred over time for implants formed in vivo, where it was observed that the porosity was lost over the course of 5 days. Implants formed in vivo had a significantly greater burst release (p < 0.05) relative to implants formed in vitro. However, during the diffusion period of release, implants formed in vitro had a significantly higher daily release (2.1%/day, p < 0.05), which correlated to changes in implant microstructure. Additionally, implants formed in vitro had a two-fold increase in the first-order degradation kinetics relative to the implants formed in vivo. These findings suggest that the changes in implant behavior occur as a result of changes in the implant microstructure induced by the external environment.