白蛋白包覆阳离子脂质纳米载体的制备及静脉注射药代动力学和组织分布

Preparation of BSA-coated cationic nanostructure lipid carriers and pharmacokinetics and biodistribution after intravenous injection

溶剂蒸发法制备普通阳离子脂质纳米载体(cNLCs)及白蛋白包覆的脂质纳米载体(BSA-cNLCs),cNLCs和BSA-cNLCs的粒径分别为69.9 nm和80 nm,电位分别为+12.5 mV和+5.02 mV。两者透射电镜照片均呈现圆整类球形结构,且BSA-cNlCs可见明显的白蛋白包覆层。紫杉醇包封率均在97%以上,载药量大于3.7%。加入血浆24 h后,cNLCs粒径增加至原来的1.7倍,而BSA-cNLCs仅增加至1.1倍,包覆白蛋白后血浆稳定性显著提高。高效液相色谱法研究大鼠体内药代动力学及荷瘤小鼠体内组织分布行为,静脉注射BSA-cNLCs 12 h后,大鼠血液中紫杉醇浓度为0.64μg/mL,而cNLCs组则无法检测到紫杉醇;BSA-cNLCs和cNLCs在荷瘤小鼠肿瘤组织中最高浓度分别为8.36μg/mL和2.52μg/mL,12 h后分别降至1.56μg/mL和0.57μg/mL。与cNLCs相比,BSA-cNLCs在血液中的滞留时间显著延长,表现出更好的长循环效果,靶向肿瘤组织的能力增加。

Common cationic nanostructure lipid carriers（cNLCs） and bovine serum albumin-coated cationic nanostructure lipid carriers（BSA-cNLCs） were prepared by solvent evaporation method.Particle size of cNLCs and BSA-cNLCs were 69.9 nm and 80 nm,with zeta potential of ＋12.5 mV and ＋5.02 mV,respectively.Both NLCs were approximately spherical in shape,and BSA layer on the surface of BSA-cNLCs was obvious.The PTX encapsulation efficiencies of both NLCs were above 97%,with drug loading efficiency of above 3.7%.After being incubated with plasma for 24 h,the particle size of cNLCs and BSA-cNLCs increased by 70% and 10%,respectively,indicating improved stability of BSA-cNLCs in comparison with cNLCs.The pharmacokinetics in rat and biodistribution in tumor-bearing mice of PTX-loaded NLCs after intravenous injection were investigated by HPLC.PTX concentration in rat blood was 0.64 μg/mL 12 h after injection of BSA-cNLCs,while no PTX could be detected in cNLCs group.In tumor-bearing mice received PTX-loaded BSA-cNLCs and cNLCs injection,cmax in tumor tissue was 8.36 μg/mL and 2.52 μg/mL,and decreased to 1.56 μg/mL and 0.57 μg/mL,respectively,12 h later.In comparison with cNLCs,the residence time in blood of BSA-cNLCs increased significantly,displaying longer circulating capability and better tumor-targeting efficiency.