College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Eur J Pharm Biopharm. 2023 Oct;191:1-11. doi: 10.1016/j.ejpb.2023.08.006. Epub 2023 Aug 12.
The objective of this study was to prepare poly(lactide-co-glycolide) (PLGA) microparticles loaded with nanosized drug by combining non-aqueous wet bead milling and microencapsulation. 200-300 nm dexamethasone, hydrocortisone and dexamethasone sodium phosphate nanosuspensions were successfully prepared by wet bead milling the drug in dichloromethane using PLGA as a stabilizer. PLGA microparticles loaded with nanosized drugs were then prepared by a solid-in-oil-in-water (S/O/W) solvent evaporation method or solid-in-oil-in-oil (S/O/O) organic phase separation method. The microparticles were characterized by laser diffraction (LD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and in vitro drug release. The nanosized drugs were homogeneously distributed within the microparticle matrix and remained crystalline, however, with a decrease in crystallinity. High drug encapsulation efficiencies >80 % were achieved at theoretical drug loadings between 5 and 30 %. Drug release profiles could be controlled by varying PLGA grades/blends, microparticle size and drug loadings. Quasi-linear release profiles without the PLGA-typical slow release phase were achieved with PLGA encapsulated nanosized drug.
本研究的目的是通过结合非水湿磨和微囊化技术来制备载纳米药物的聚（丙交酯-共-乙交酯）（PLGA）微球。通过在二氯甲烷中使用 PLGA 作为稳定剂将药物湿磨，成功制备了 200-300nm 的地塞米松、氢化可的松和地塞米松磷酸钠纳米混悬剂。然后通过固-油-水（S/O/W）溶剂蒸发法或固-油-油（S/O/O）有机相分离法制备载纳米药物的 PLGA 微球。通过激光衍射（LD）、扫描电子显微镜（SEM）、透射电子显微镜（TEM）、差示扫描量热法（DSC）、X 射线粉末衍射（XRPD）和体外药物释放对微球进行了表征。纳米药物均匀分布在微球基质中，保持结晶状态，但结晶度降低。在理论药物载量为 5%至 30%之间，实现了高药物包封效率>80%。通过改变 PLGA 等级/共混物、微球粒径和药物载量，可以控制药物释放曲线。使用 PLGA 包封的纳米药物可实现准线性释放曲线，而无 PLGA 典型的缓慢释放阶段。
