State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Shenyang Agriculture University, Shenyang, Liaoning 110161, People's Republic of China.
J Colloid Interface Sci. 2016 Sep 15;478:46-53. doi: 10.1016/j.jcis.2016.05.045. Epub 2016 May 24.
A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens.
一种新的策略被开发出来，用于制备具有窄粒径分布的多孔微球，以控制肽的释放，该策略涉及在不使用任何致孔剂的情况下制备多孔微球，然后进行孔封闭过程。使用具有不同疏水区段的两亲性聚合物（聚（单甲氧基聚乙二醇-co-d,l-丙交酯）（mPEG-PLA）、聚（单甲氧基聚乙二醇-co-d,l-乳酸-co-乙醇酸）（mPEG-PLGA））作为微球基质，通过双乳液-预混膜乳化技术与溶剂蒸发法相结合，制备多孔微球。两种微球都具有窄的粒径分布和多孔表面，这主要是由于（a）亲水性聚乙二醇（PEG）段吸收水分子，然后进行水蒸发过程，以及（b）由于二氯甲烷（MC）的快速蒸发，微球局部爆炸。重要的是，mPEG-PLGA 微球具有蜂窝状结构，而 mPEG-PLA 微球内部具有实心结构，这表明不同的疏水区段可以调节溶剂与基质聚合物之间的亲和力，并影响微球基质的相分离速率。通过封闭孔的微球来展示长期释放模式，这些微球是由装载鲑鱼降钙素（SCT）的 mPEG-PLGA 微球制备的。这些结果表明，使用永久几何模板作为新的致孔剂构建用于药物持续释放的多孔微球具有潜力。
