红细胞膜包裹的聚多巴胺载补骨脂二氢黄酮甲醚纳米粒的制备及其药代动力学
Preparation and pharmacokinetics of polydopamine-loaded bavachinin nanoparticles coated with erythrocyte membrane
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摘要: 利用聚多巴胺（PDA）为载体，通过物理吸附作用高效负载补骨脂二氢黄酮甲醚（BVA），进一步利用红细胞膜进行修饰，构建红细胞膜仿生纳米粒（RBC-BP），延长其在体内的驻留时间并研究其药代动力学过程。采用溶剂置换法制备负载BVA的PDA纳米粒（BP），以吸附率为评价指标，考察PDA负载BVA的影响因素；提取分离红细胞膜，采用孵育共挤出法制备RBC-BP，考察pH对膜包覆的影响，挤出次数对RBC-BP的粒径和均一性的影响；对RBC-BP的粒径、电位、形态及累积释放率进行系统表征，初步探讨其药代动力学特征。结果表明，当PDA与BVA之比为1∶0.5、溶液pH为7、孵育时间为6 h、孵育温度为20 ℃ 时，BP吸附率高达（92.08 ± 0.17）%，载药率为（42.05 ± 2.95）%；当pH为4时，红细胞膜可通过电荷作用成功定向包覆在BP表面。体外研究表明，RBC-BP具有明显的核壳结构，粒径（308.63 ± 6.56）nm，稳定性好；体内药代动力学研究显示，RBC-BP可以延长纳米粒在体内的循环时间。Abstract: Polydopamine (PDA) nanoparticles were prepared as a carrier, and bavachinin (BVA) was efficiently loaded by physical adsorption.The erythrocyte membrane was further utilized to modify and construct the erythrocyte membrane biomimetic nanoparticles (RBC-BP), the residence time in the body was extended and the in vivo analytical method was established to investigate their pharmacokinetics in mice.Polydopamine nanoparticles loaded with BVA (BP) were prepared by solvent replacement method, and the influencing factors of PDA loaded with BVA were investigated with the adsorption rate as the evaluation index.The erythrocyte membrane was extracted and separated, and RBC-BP was prepared by incubation coextrusion method. The effects of pH value on membrane coating and the extrusion times on the particle size and uniformity of RBC-BP were investigated.The particle size, potential, morphology, and cumulative release rate of RBC-BP were systematically characterized, and their pharmacokinetics in mice were preliminarily explored.The results showed that the adsorption rate of BP was as high as (92.08 ± 0.17) % and the drug loading rate was (42.05 ± 2.95) % at the PDA to BVA ratio of 1∶0.5, the solution pH value of 7, the incubation time of 6 h, and the incubation temperature of 20 °C, and that the erythrocyte membrane could be successfully oriented and coated on the surface of BP by the action of electric charge at the pH value of 4. The in vitro studies showed that RBC-BP has the apparent core-shell structure with the particle size of (308.63 ± 6.56) nm and good stability, and in vivo pharmacokinetic studies showed that RBC-BP can significantly extend the circulation time of nanoparticles in vivo.
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