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目的:进行叶酸(FA)受体介导盐酸小檗碱长循环脂质体的制备与动物体内药效学研究,探讨其作用特点及其可能的作用机制。方法:在胆固醇上引入丁二酸酐,便于其通过酰胺键与FA-PEG上氧基结合,进而通过硫酸铵梯度法制备叶酸介导主动靶向盐酸小檗碱脂质体。BALAB/cA裸小鼠接种人肺癌SPC-A4细胞株,被动靶向小檗碱脂质体组、被动靶向小檗碱脂质体组(含游离叶酸)、主动靶向小檗碱脂质体组、主动靶向小檗碱脂质体组(含游离叶酸)、盐酸伊立替康注射液组均按40mg·kg~(-1)给药,连续静脉给药3周,停药观察1周后脱颈椎处死,解剖取瘤块,称质量。测定叶酸介导主动靶向盐酸小檗碱脂质体在小鼠体内肿瘤抑制率。结果:该合成方法可以得到纯度很高的目标产物。叶酸介导盐酸小檗碱脂质体组较无叶酸介导的盐酸小檗碱脂质体组肿瘤抑制效果好,进一步证实叶酸主动与叶酸受体(FR)结合并引导抗癌药物主动攻击肺癌细胞;叶酸介导盐酸小檗碱脂质体组较叶酸介导盐酸小檗碱脂质体(含游离叶酸)对肿瘤抑制率高,原因是游离的叶酸竞争性地占据了叶酸受体与肿瘤细胞结合的位点。结论:叶酸介导盐酸小檗碱脂质体对人肺癌SPC-A4小鼠异体移植瘤有明显的肿瘤抑制率,叶酸受体介导盐酸小檗碱长循环脂质体有很好的市场开发前景,将可能为肺癌患者提供一种更有效的治疗选择。
OBJECTIVE: To study the preparation of folic acid (FA) receptor mediating berberine hydrochloride long-acting liposomes and their pharmacokinetics in vivo, and to explore their roles and possible mechanisms. METHODS: Succinic anhydride was introduced into cholesterol to facilitate its binding to the oxy group on FA-PEG through amide bond. Folic acid-mediated active targeted berberine hydrochloride liposomes were prepared by ammonium sulfate gradient method. BALB / cA nude mice inoculated with human lung cancer SPC-A4 cell line, passive target berberine liposome group, passive target berberine liposome group (containing free folic acid), active target berberine lipid Body group, active targeted berberine liposome group (containing free folic acid), irinotecan hydrochloride injection group were given 40mg · kg -1, continuous intravenous administration for 3 weeks, withdrawal observed 1 A week after the cervical spondylosis, anatomy to take tumor mass, said the quality. Folic acid-mediated active targeting of berberine hydrochloride liposome in mice in vivo tumor inhibition rate. Results: The synthesis method can get high purity of the target product. Folic acid-mediated berberine hydrochloride liposome group than the non-folate-mediated berberine hydrochloride liposome tumor inhibition effect, and further confirmed that folic acid and folate receptor (FR) and lead the active anti-cancer drugs to actively attack lung cancer Folic acid-mediated berberine hydrochloride liposomes group compared with folic acid-mediated berberine hydrochloride liposomes (including free folic acid) on tumor inhibition rate is high, due to the free folate competing to occupy the folate receptor and tumor Site of cell binding. CONCLUSION: Folic acid-mediated berberine hydrochloride liposomes have obvious tumor inhibition rate on human lung cancer SPC-A4 mice xenografts and folate receptor mediated long circulating berberine hydrochloride liposomes have good market development Prospects will likely provide lung cancer patients with a more effective treatment option.