淫羊藿苷/载明胶纳米复合物-PLGA缓释系统的制备及工艺优化

目的：制备淫羊藿苷（ICA）@明胶纳米粒（GNPs）-聚乳酸-羟基乙酸共聚物（PLGA）（ICA@GNPs-PLGA）缓释系统，并对制备工艺进行优化。方法：采用二步去溶剂法和S/O/W乳化溶剂挥发法制备ICA@GNPs-PLGA缓释系统，检测投放的PLGA和纳米复合物的质量比和ICA的投入量等不同因素对微球包封率（EE）的影响以优化制备工艺。扫描电镜（SEM）观察纳米复合物和微球的表面特征；高效液相色谱法（HPLC）测量微球EE及其体外释放结果。结果：所制备的复合微球和纳米复合物均为白色粉末状；SEM下微球和纳米复合物表面光滑、圆整，粒径较为均一，粒径分布范围分别为4~12 μm和150~200 nm。当GNPs投入量为6 mg，PLGA在二氯甲烷（DCM）中的临界浓度为0.5%~1.0%；当GNPs的质量上升至12 mg时，PLGA在DCM中的临界浓度升至1.0%~2.0%；当PLGA的浓度低于0.25%时，无完全包封的复合微球可以形成。在临界浓度内，ICA@GNPs-PLGA微球的EE高于（62.00±1.25）%，且EE和ICA的投入量呈负相关关系（P<0.05）。24h时内微球累积释放率低于5.47%，40d时累积释放率为65.21%。结论：采用优化的制备工艺可以制备出粒径分布较窄、载药率较高、低突释和长期释放的ICA@GNPs-PLGA微球缓释系统。

Preparation of icariin/gelatin nanocomposite-PLGA sustained release system and its optimization of technology

Objective:To prepare the sustained release system of icariin(ICA)@ gelatin nanoparticles (GNPs)-polyactic-co-glycolic acid(PLGA)(ICA @ GNPs-PLGA), and to optimize the conditions. Methods:ICA@GNPs-PLGA sustained release system was prepared using two-step desolvation method and S/O/W emulsion solvent-evaporation technique.The effects of different conditions,such as the PLGA:GNPs mass ratio and the total quality of ICA added on the entrapment efficiency(EE)of ICA@GNPs-PLGA composite microspheres were detected to optimize the preparation process. The surface morphology of GNPs and ICA@GNPs-PLGA composite microspheres were observed by SEM.The EE and the release results of ICA@GNPs-PLGA in the sample were determined with HPLC.Results:The prepared composite microspheres and nanocomplex were were white powder.The SEM results showed that the composite microspheres and nanocomplexs were spherical,the surfaces were smoothy,and the particle size distribution range was 4-12 μm and 150-200 nm,respectively,relatively uniform.At a GNPs mass fraction of 6 mg,the critical concentration of PLGA in DCM ranged within 0.5%-1.0%.At a GNPs mass fraction of 12 mg,the critical concentration of PLGA in DCM ranged within 1.0%-2.0%.However,at a critical PLGA mass fraction lower than 0.25%,no fully formed composite microspheres were observed.Within the critical concentration,the average EE of ICA@GNPs-PLGA microspheres was higher than(62.00±1.25)%.In addition,the EE of ICA in the microspheres was negatively correlated with the quality of ICA added.The accumulative release rate was less than in 24 h and it was 65.21% in 40 d.Conclusion:The ICA@GNPs-PLGA microspheres with homogeneous particle size distribution,high EE,low initial burst and without agglomeration can be acquired under the optimized conditions.