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

Formulations of a polymeric delivery system containing a 75/25 poly(DL-lact ide-co-caprolactone dissolved in either N-methyl-2-pyrrolidone or dimethyl sulfoxide were injected both subcutaneously (SC) and intramuscularly (IM) i nto rhesus monkeys. Each monkey received an SC and IM injection of each of the two formulations, for a total injection volume of 4 mt. The monkeys wer e observed daily for overt signs of toxicity, and after 4 weeks biopsies of each implant site were fixed, stained, and evaluated histologically for ti ssue reaction to the polymer system. Tissue response was graded upon the pr esence and level of fibrous connective tissue and inflammatory cell infiltr ate. The polymer formulations appeared to be safe, as the animals remained healthy and active throughout the study with no changes in food or water co nsumption, weight loss, or abnormal behavior observed. Tissue response to b oth formulations was considered mild and similar to that for other biodegra dable polymers, in that the reaction was limited to tissue immediately adja cent to the residual polymer fragments and consisted of a mild fibroplasia with the presence of a few lymphocytes and macrophages. There were no diffe rences between the two formulations in tissue response, and both formulatio ns were considered acceptable for use as injectable implant systems. (C) 19 99 John Wiley & Sons, Inc.