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

摘要

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).24 h时内微球累积释放率低于5.47%,40 d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.%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.