THE EFFECT OF PHAGOCYTOSIS OF POLY(L-LACTIC ACID) FRAGMENTS ON CELLULAR MORPHOLOGY AND VIABILITY

The aim of this study was to investigate the effect of phagocytosed poly(L-lactic acid) particles on the morphology and viability of phagocytes, mainly macrophages. Therefore, predegraded poly(L-lactic acid) (P-PLLA) and nontreated PLLA (N-PLLA) particles, both having diameters not exceeding 38 mu m, were injected intraperitoneally in mice. P-PLLA particles were obtained by 25 kGy gamma-irradiation of N-PLLA particles. N-PLLA and P-PLLA particles were injected using an 0.3% ethanol/0.90% saline solution intraperitoneally to the mice. We also studied the release of the absorbed ethanol as a possible model for the release of low molecular weight, potentially toxic products. As control, nondegradable polytetrafluoroethylene (PTFE) particles and the carrier solution were used. After 1, 2, 3, 4, 5, and 7 days, the cells of the abdominal cavity were harvested to study the effect of phagocytosis of polymer particles on phagocytic cell morphology and viability. Studies with transmission electron microscopy indicated that, upon injection of particles in the peritoneal cavity, macrophages demonstrated signs of cell damage, cell death, and cell lysis due to phagocytosis of a large amount of P-PLLA particles. The morphology of the cells that had phagocytosed the N-PLLA and PTFE particles did not differ substantially from those of control animals in which only the solution was injected. Also, in the controls, hardly any cell death and no debris was observed. When the PLLA particles were injected as a suspension in a 0.3% ethanol/0.90% saline solution, no difference was observed between N-PLLA and P-PLLA. After phagocytosis, both cause cell damage, sometimes leading to cell death. The highest numbers of necrotic cells were observed on day 2. The effects could be caused by the (peak) release of degradation products from P-PLLA fragments or by the release of the absorbed ethanol when the 0.3 ethanol/0.9 saline solution was used to administer the particles. In conclusion, it can be stated that cell damager sometimes leading to cell death, may be caused by phagocytosed poly(L-lactic acid) particles. (C) 1993 John Wiley and Sons, Inc.