摘要
目的以阿霉素(DOX)为模型药物,以B7-H3免疫脂质体为载体,构建载DOX免疫长循环脂质体(BPDL),并评价其在SD大鼠体内的药动学行为以及对人乳腺癌MCF-7细胞的毒性作用。方法采用薄膜分散法制备包载DOX的脂质体BPDL,通过透射电镜观察其微观形态,激光粒度仪测定粒径分布及zeta电位。采用透析法考察其体外释药情况,并以SD大鼠为模型评价体内药动学,比较DOX、DOX-Lips和BPDL在体外对人乳腺癌MCF-7细胞的毒性作用。结果BPDL呈类球状分布,平均粒径为152.27 nm,电位为-25.9 mV,载DOX量为8.16%±0.08%。BPDL在磷酸缓冲溶液中释放96 h时,DOX的累积释放率为60.15%。与原料药比较,BPDL脂质体的MRT、C_(max)、CLz升高,其中的DOX的t_(1/2)比游离药物组延长3.59倍(P<0.05);细胞毒性实验中BPDL中DOX的浓度为160μg·mL^(-1)时,给药72 h条件下,对MCF-7抑制率达到97.48%。结论本研究制备的偶联B7-H3抗体的免疫长循环脂质体可延长药物在血液中的循环时间,对人乳腺癌细胞具有较强的抑制效果,为开发化疗联合免疫治疗方法提供了新的科研思路。
Objective Doxorubicin(DOX)was used as the model drug and B7-H3 immune liposome was used as the carrier to construct the DOX-carrying immune long-circulating liposome(B7-H3-PEG-DOX-Lips,BPDL),and the pharmacokinetic behavior of BPDL in SD rats and its toxic effect on human breast cancer MCF-7 cells were evaluated.Methods The DOX-containing liposome BPDL was prepared by thin film dispersion method.The microscopic morphology of BPDL was observed by transmission electron microscope.The particle size distribution and zeta potential were determined by laser particle size analyzer.The in vitro drug release was investigated by dialysis,and the in vivo pharmacokinetics were evaluated using SD rats as models to compare the toxic effects of DOX,DOX-Lips and BPDL on human breast cancer MCF-7 cells in vitro.Results The average particle size of BPDL was 152.27 nm,the potential was-25.9 mV,and the DOX loading was 8.16%±0.08%.When BPDL was released in phosphate buffer solution for 96 h,the cumulative release rate of DOX was 60.15%.Compared with the bulk drug,MRT,C_(max) and CLz of BPDL liposomes were increased,and the t_(1/2) of DOX was 3.59 times longer than that of free drug group(P<0.05).In the cytotoxicity experiment,when the concentration of DOX in BPDL was 160μg·mL^(-1),the inhibition rate of MCF-7 reached 97.48%under the condition of 72 h of administration.Conclusion The long-circulating liposome conjugated with B7-H3 antibody prepared in this study can prolong the circulation time of drugs in the blood,and has a strong inhibitory effect on human breast cancer cells,providing a new scientific research idea for the development of chemotherapy combined with immunotherapy.
作者
衣琪昆
张新宇
袁辉
梁家文
李士壮
阎雪莹
YI Qikun;ZHANG Xinyu;YUAN Hui;LIANG Jiawen;LI Shizhuang;YAN Xueying(Heilongjiang University of Chinese Medicine,Harbin 150040,China)
出处
《药学研究》
CAS
2024年第9期854-861,870,共9页
Journal of Pharmaceutical Research
基金
黑龙江省自然科学基金项目(No.LH2021H102)。
