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 microns, 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/0.9% 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/0.9% saline solution, no difference was observed between N-PLLA and P-PLLA. After phagocytosis, both cause cell damage, sometimes leading to cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of porosity on the degradation rate of poly(L-lactic acid) (PLLA) films was investigated in vitro and in vivo. Non-porous, porous and "combi'" (porous with a non-porous layer) PLLA films were used. Changes in Mw, Mn, polydispersity (Mw/Mn) ratio, melting temperature (Tm), heat of fusion, tensile strength, E-modulus, mass and the remaining surface area of cross-sections of the PLLA films were measured. In general, during the degradation process, the porous film has the highest Mw, Mn, Mw/Mn ratio and Tm, while the nonporous film has the lowest. In contrast, the highest heat of fusion values were observed for the non-porous film, indicating the presence of relatively smaller molecules forming crystalline domains more easily. The tensile strength and E-modulus of the non-porous film decrease faster than those of the porous and the combi film. None of the three types of films showed massive mass loss in vitro nor a significant decrease in remaining polymer surface area in light microscopical sections in vitro and in vivo. Heavy surface erosion of the non-porous layer of the combi film was observed after 180 days, turning the combi film into a porous film. This is also indicated by the changes in tensile strength, Mw, Mw/Mn, Tm and heat of fusion as a function of time. It is concluded that non-porous PLLA degrades faster than porous PLLA. Thus, in our model, porosity is an important determinant of the degradation rate of PLLA films.
This letter describes the preparation of quinoline derivatives and their cytotoxic potentials toward human carcinoma cell lines. Among the selected compounds, 8-hydroxy-2-quinolinecarbaldehyde (3) showed the best in vitro cytotoxicity against the human cancer cell lines, including MDA231, T-47D, Hs578t, SaoS2, K562, SKHep1 (with a MTS 50 range of 12.5−25 μg/mL) and Hep3B (with a MTS 50 range of 6.25±0.034 μg/mL). The in vivo antitumor activity of compound 3 on subcutenaous Hep3B hepatocellular carcinoma xenograft in athymic nude mice was then studied. The results showed that the dose of 10 mg/kg/day of compound 3 with intraperitoneal injection for 9 days totally abolished the growth of the xenograft tumor of Hep3B with no histological damage on vital organs as compared with the control. The experimental results suggested that compound 3 has a good potential as an antitumor agent.
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