Sirolimus-loaded biodegradable implants induce long lasting anti-inflammatory and antiangiogenic effects

Abstract Sirolimus is an immunosuppressive drug with activity in rheumatoid arthritis through inhibition of mTOR and T-lymphocytes activation and proliferation. However, its side effects limit usefulness. In this study, we developed sirolimus-loaded biodegradable implants, evaluated in vivo release of the drug and anti-inflammatory and antiangiogenic activities. Implants containing sirolimus were inserted into the subcutaneous tissue of mice and drug released was determined during 42 days. Histology of the skin and subcutaneous tissue close to the implanted site was performed after 7 and 42 days. The antiangiogenic activity of sirolimus implants was evaluated in the chorioalantoic membrane (CAM) from chicken eggs. The mice model of fibrovascular tissue growth induced by implantation of a subcutaneous cotton pellet was used to evaluate anti-inflammatory activity. Sirolimus implant promoted a slow release of the drug during 42 days. Histology did not show signs of intense local inflammatory response at the site of implantation. Sirolimus implants reduced vessels formation in the CAM and proliferation of fibrovascular tissue. Concluding, sirolimus-loaded implants reduced angiogenesis and chronic inflammatory response in the models evaluated. This preliminary study indicates that the implants are safe to the experimental animals and that they may represent a promising alternative for the treatment of chronic inflammation.