基于普朗尼克双配体修饰的载药纳米靶向聚合物胶束制备工艺的筛选及靶向性评价  

Selection and targetability of the preparation process of load drug nanotargeting polymer micelles modified with dual ligand by pluronics

作　　者：高欢 尹东锋 GAO Huan;YIN Dong-feng(School of Pharmacy,Xinjiang Medical University,Urumqi 830011,China;General Hospital of Xinjiang Military Region,Urumqi 830000,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830011 [2]解放军新疆军区总医院,乌鲁木齐830000

出　　处：《军事医学》2021年第8期614-619,631,共7页Military Medical Sciences

摘　　要：目的优选载多柔比星(阿霉素,DOX)纳米靶向聚合物胶束的制备工艺,并对其体外释放行为和体外靶向性进行考察。方法以琥珀酰亚胺法合成靶向聚合物材料,以包封率、载药量和总评归一化值为评价指标,利用星点设计-响应面法优化薄膜水化法设计考察投药量、有机溶剂体积、水化体积对纳米胶束制备的影响,并优选处方。以与羟基磷灰石(HA)和离体骨片共同孵育考察骨靶向性;以乳腺癌细胞(MDA-MB-231)为模型做体外细胞摄取考察肿瘤细胞靶向性。结果成功合成靶向聚合物材料P123-ALN和P123-DP-8,优选纳米胶束最佳制备工艺为:DOX投药量5.48 mg,有机溶剂体积7.28 ml,水化体积8.58 ml。根据筛选出的最佳制备工艺,确定混合载体材料的比例为4∶1时,制备的双配体修饰的纳米靶向聚合物胶束P123-ALN/P123-DP-8@DOX符合纳米制剂的制备要求,包封率为76.97%,载药量3.70%,粒径122.97 nm,ζ电位-12.60 mV,缓释和体外靶向性良好。结论用最优处方制备的纳米靶向聚合物胶束可为后续骨靶向给药奠定基础。Objective To optimize the preparation process of doxorubicin(DOX)-loaded nano-targeting polymer micelles,and to investigate the release behavior and targetability in vitro.Methods Targeting polymer materials were synthesized using the succinimide method.With the encapsulation efficiency,drug loading and overall desirabilities as indexes of evaluation,the central composite design response-surface method was adopted to optimize the design of the thin film hydration method in order to investigate the effects of DOX dosage,organic solvent volume,and hydration volume on the preparation of nanomicelles.The bone targetability was investigated by incubating hydroxylapatite(HA)along with isolated bone pieces.Cells in vitro were cultivated using MDA-MB-231 as a model to assess the targetability of tumor cells.Results The targeted polymer materials P123-ALN and P123-DP-8 were synthesized,and the optimal preparation process of nanomicelles was optimized as follows:DOX dosage was 5.48 mg,the organic solvent volume was 7.28 ml,and the hydration volume was 8.58 ml.When the ratio of mixed carrier materials was 4∶1,the prepared dual-ligand modified nano-targeting polymer micelles P123-ALN/P123-DP-8@DOX met the preparation requirements of nano-formulations.The encapsulation efficiency was 76.97%,drug loading was 3.70%,particle size was 122.97 nm,zeta potential was-12.60 mV,and sustained release and in vitro targetability were desirable.Conclusion The nano-targeting polymer micelles prepared with the optimal prescription can facilitate subsequent bone-targeted drug delivery.

关 键 词：星点设计 纳米胶束 工艺优化 归一化值 

分 类 号：R944[医药卫生—药剂学]