Antibiotic in vivo/in vitro release, histocompatibility and biodegradation of gentamicin implants based on lactic acid polymers and copolymers

Abstract

Biodegradable implants containing 10 mg of gentamicin each were prepared by compressing the polymer-drug mixture. The liberation of gentamicin from the implants and the biodegradation of the implants were investigated by following in vitro and in vivo experiments. Implants based on pure poly( l-lactic acid) (L-PLA) released the incorporated antibiotic throughout 30 days with a decreasing delivery rate. During the first 24 h L-PLA implants released a total amount of 3600 μg gentamicin. Within 14 days the release rate had decreased to about 12 μg/day. The release profile of implants based on dl-lactic acid-glycolic acid copolymer (RG 502) was completely different. About 1900 μg were released from the copolymer implants during the first 24 h. Release rate decreased to a value of about 3 μg/day 15 days after implantation. In a second phase, starting 20 days after implantation, drug delivery increased again to reach values of about 100 μg/day at the end of the experiment, i.e. 28 days after implantation. Very good tissue compatibility arises from the absence of inflammatory reactions throughout the entire time of implantation as shown by microscopy examinations. The developed implants based on biodegradable polymers are suited for the treatment of acute and chronic bone and tissue infections due to their specific release profiles, their excellent histocompatibility and their biodegradability.