Biocompatibility of a biodegradable in situ forming implant system in rhesus monkeys

Formulations of a polymeric delivery system containing a 75/25 poly(DL-lactide-co-caprolactone dissolved in either N-methyl-2-pyrrolidone or dimethyl sulfoxide were injected both subcutaneously (SC) and intramuscularly (IM) into rhesus monkeys. Each monkey received an SC and IM injection of each of the two formulations, for a total injection volume of 4 mL. The monkeys were observed daily for overt signs of toxicity, and after 4 weeks biopsies of each implant site were fixed, stained, and evaluated histologically for tissue reaction to the polymer system. Tissue response was graded upon the presence and level of fibrous connective tissue and inflammatory cell infiltrate. The polymer formulations appeared to be safe, as the animals remained healthy and active throughout the study with no changes in food or water consumption, weight loss, or abnormal behavior observed. Tissue response to both formulations was considered mild and similar to that for other biodegradable polymers, in that the reaction was limited to tissue immediately adjacent to the residual polymer fragments and consisted of a mild fibroplasia with the presence of a few lymphocytes and macrophages. There were no differences between the two formulations in tissue response, and both formulations were considered acceptable for use as injectable implant systems.