Construction Of Porous PLGA Microspheres And Its Application In Biomedicine

Porous microspheres have interconnected porous structures with high porosity,high specific surface area,and easy to fabricate and modify.They are not only good microcarriers for three-dimensional cell culture,but also can be used as drug-loaded embolic agents.As a microcarrier for cell culture,porous microspheres have high specific surface area,which is conducive to large-scale cell culture,and can provide three-dimensional growth environment for cells,so that the normal function and vitality of cells can be maintained.As a chemotherapeutic embolization agent,drug-loaded porous microspheres can not only physically embolized the supplying arteries of the tumor,but also locally sustained-release chemotherapeutic drugs,which improves the anti-tumor effect and reduces the side effects of chemotherapeutic drugs.Poly（lactic-co-glycolic acid）（PLGA）has good biocompatibility,ball-forming,film-forming properties,easy to fabricate and modify,and has been widely used in clinic.In this paper,porous microspheres and drug-loaded porous microspheres were controllablely constructed based on PLGA,and their in vitro and in vivo properties as cell microcarriers and interventional embolization agents were studied.The main experimental research and results are as follows:（1）Porous PLGA microspheres were prepared by double emulsion and gas foaming method.The morphology and particle size of porous PLGA microspheres were adjusted by adjusting the ratio of PLGA/dichloromethane（DCM）and the concentration of NH₄HCO₃.The obtained porous microspheres have an internally connected porous structure and the particle size distribution is between 10～600μm.（2）The biocompatibility of porous PLGA microspheres was evaluated,including cell compatibility,blood compatibility and histocompatibility.The experimental results showed that porous PLGA microspheres had good biocompatibility.Human vascular smooth muscle cells（HVSMCs）and human umbilical vein endothelial cells（HUVECs）were inoculated on the surface of porous microspheres,and it was observed that both kinds of cells could adhere and grow on the surface of microspheres.（3）Paclitaxel（PTX） was loaded in PLGA porous microspheres by physical embedding.The drug loading of PTX loaded porous PLGA microspheres was controlled by adjusting the ratio of PLGA/PTX,and the physicochemical properties of the microspheres were characterized.The drug loading,encapsulation efficiency and drug release curve of PTX loaded porous PLGA microspheres were determined.The experimental results showed that the particle size distribution of drug-loaded porous microspheres was between 50～600μm.Drug crystals were observed on the surface of drug-loaded microspheres.With the increase of PTX content,the drug loading and encapsulation efficiency of drug-loaded porous microspheres increased,and the cumulative drug release at the same time increased.The drug-loaded porous microspheres with different PLGA/PTX ratios can release PTX stably and slowly.In vitro antitumor activity test showed that the drug-loaded porous microspheres had good antitumor activity in vitro on human breast cancer cell MCF-7 and human liver cancer cell HepG2.