In vitro and in vivo evaluation of the effects of PLA microparticle crystallinity on cellular response

Abstract

Previous research suggests that crystallinity of poly( l-lactide) P(L)LA microparticles can influence surface free energy, which in turn might influence biocompatibility. This work studies the cellular response to P(L)LA microparticles of different crystallinity both in vitro and in vivo. Following incubation with P(L)LA microparticles, the in vitro production of reactive oxygen intermediates (ROI) was measured as a marker of cellular response. In both fluorescence and chemiluminescence experiments to measure ROI, a small effect of microparticle crystallinity on NR8383 AM response was observed. Microparticles of higher crystallinity elicited a smaller inflammatory response compared to lower crystallinity particles. Compared to the elevated inflammatory response induced by zymosan, the response to all P(L)LA microparticles tested was practically negligible. Results from in vivo experiments further supported conclusions that P(L)LA microparticles elicit minimal inflammatory response. Following acute exposure to P(L)LA microparticles in guinea-pig lungs, the inflammatory response was not significantly different from the response observed when sterile saline was administered. In contrast to the in vitro experiments, there were not apparent differences in cellular responses to microparticles of different crystallinity.