目的 制备载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物(PEG-PLGA)纳米粒(H102-NP), 考察其体内外特性。方法 采用正交设计法优化纳米粒的处方及制备工艺, 并对载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物的形态、粒径、Zeta电位、包封率、体外释药及稳定性进行表征;小鼠尾静脉注射载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物, 液质联用测定血和脑中药物浓度。结果 载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物呈球状、均一性好, 平均粒径为137 nm, Zeta电位为-38 mV, 包封率为64%。载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物在pH 7.4 PBS和血浆中12 d累积释放分别为93%和95%。载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物与血浆及脑匀浆孵育12 h, 药物降解约5%。静注H102肽溶液, 血中消除快, 脑内含量低;而将其载于纳米粒中, 药物血中消除减慢, 且脑内H102浓度较高、维持时间较长。载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物在血和脑内AUC值分别是溶液剂的245倍和11倍。结论 所制备的载H102肽的聚乙二醇-聚乳酸-羟基乙酸共聚物具有良好的体内外特性, 有望应用于阿尔茨海默病的治疗。

OBJECTIVE To prepare H102 loaded PEG-PLGA nanoparticles (H102-NP) and investigate its properties in vitro and in vivo. METHODS Orthogonal design was used to optimize the formulation. The nanoparticles were characterized in terms of morphology, size, Zeta potential, drug encapsulation efficiency, in vitro release and stability. H102 concentrations in plasma and brain following tail vein injection of H102-NP in mice were measured by LC-MS. RESULTS H102-NP were spherical and of regular size. The average size, Zeta potential and encapsulation efficiency of H102-NP were found to be around 137 nm, -38 mV and 64%. The cumulative release of H102-NP in pH 7.4 PBS and plasma at 12 d is 93% and 95%, respectively. Incubated in plasma and brain homogenate at 37 ℃ for 12 h, the degradation of H102 encapsulated in nanoparticles was only 5%. Compared with H102 solution which was eliminated rapidly in blood with low concentration in brain, H102-NP was eliminated slowly in blood with higher concentration and longer duration in brain after intravenous administered in mice. The AUC of H102-NP was 245 times and 11 times higher in plasma and brain than that of H102 solution. CONCLUSION H102- loaded nanoparticles are successfully prepared with good properties in vitro and in vivo, which showed a prospect for the treatment of Alzheimer′s disease.