多西环素纳米脂质体缓释凝胶生物相容性及细胞毒性

目的评价自制多西环素纳米脂质体缓释凝胶的生物相容性,及对体外培养小鼠成纤维细胞的毒性。方法选取体外培养的小鼠成纤维细胞L-929,采用琼脂覆盖试验,根据倒置显微镜下观察和计算的培养不同时间点L-929细胞的平均褪色指数和溶解指数,评价样品的细胞毒性分级情况。以最大剂量法,于白色豚鼠背部对称部位分别进行注射诱导和敷贴激发致敏,观察激发后48h内皮肤红斑和水肿反应程度。SD大鼠用20%样品水溶液连续灌胃7d,观察临床症状并计算食物利用率。结果L-929细胞环素纳米脂质体缓释凝胶培养不同时间点的细胞毒性分级为1(阴性对照为0)。致敏试验显示,48h内白色豚鼠背部皮肤无明显红斑和水肿反应。SD大鼠经样品灌胃7d后,无毒性反应表现;与等量蒸馏水灌胃的对照组比较,体质量和食物利用率无明显差异。结论多西环素纳米脂质体缓释凝胶无潜在细胞毒性及致敏作用,是一生物相容性良好的牙周缓释制剂。

Biocompatibility and cytotoxicity of doxycycline nano-liposome sustained-release gel

Objective To evaluate the biocompatibility of self-prepared doxycycline nano-liposome sustained-release gel and its cytotoxicity on mice fibroblasts cultured in vitro. Methods Mice fibroblasts L-929 cultured in vitro were selected, and agar overlay assay was adopted. The average discoloration index and lysis index at different culture time points were obtained by inverted microscopy, and the cytotoxicity grade was determined. Injection-induced and application-induced sensitization were performed with maximum dose at the symmetrical sites of the back of albino guinea-pigs, respectively, and the skin erythema and edema were evaluated within 48 h. Intragastric administration of 20% sample water solution was conducted on SD rats for 7 consecutive days, and the clinical manifestations were observed and food utilization rate was calculated. Results The cytotoxicity was graded 1 for the L-929 fibroblasts cultured on doxycycline nano-liposome sustained-release gel (the negative control was graded 0). It was revealed by the sensitization test that there was no obvious skin erythema and edema at the back of albino guinea-pigs. After intragastric administration of sample water solution for 7 days, no toxic reaction was found. Compared with the control group intragastrically administered with same amount of distilled water, there was no difference in body weight and food utilization rate. Conclusion Doxycycline nano-liposome sustained-release gel, which has no potential cytotoxicity and sensitization, is a sustained-release periodontal preparation with excellent biocompatibility.