A new bioerodible polymer insert for the controlled release of metronidazole.

Abstract

This study evaluates a new class of bioerodible polymers as periodontal inserts for the controlled release of metronidazole. The system is based on association polymers formed from compatible blends of cellulose acetate phthalate (CAP) and a hydrophobic block copolymer of polyoxyethylene and polyoxypropylene, Pluronic L101. In addition to characterizing these polymers by thermal analysis, their erosion and metronidazole release characteristics were determined both in vitro, and in vivo using a rat model. The results show that increasing the concentration of Pluronic L101 in the blend to 50% and above leads to a sharp reduction in the rates of polymer erosion and metronidazole release. The characteristics of these slowly eroding films are potentially suitable for use as periodontal drug inserts with an effective duration of up to several days. Depending on the blend composition, the mechanism of metronidazole release was found to range from a surface erosion-controlled process to an erosion-modulated diffusion process. In all in vivo experiments, no signs of adverse tissue reactions were detected. Based on these results, prototype delivery inserts were designed and subsequently evaluated in volunteer patients. Preliminary results from this pilot study show that the metronidazole concentration in the gingival crevicular fluid was significant throughout the sampling period of up to 3 hr and remained well above the minimum inhibitory concentration for most periodontal pathogens. In addition, no discomfort or irritation was reported by the test subjects.