Development of uniform fenofibrate-loaded biodegradable microparticle by membrane emulsification.
Development of uniform fenofibrate-loaded biodegradable microparticle by membrane emulsification.
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通过膜乳化法开发均匀的非诺贝特负载可生物降解微粒。
DOI：
10.1016/j.ijpharm.2023.123675
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发表时间：
2024
影响因子：
5.8
通讯作者：
Xu,Qingguo
中科院分区：
文献类型：
--
作者：
Meng,Tuo;Sudarjat,Hadi;Momin,Mohammad;Ma,Jian-Xing;Xu,Qingguo
非诺贝特对糖尿病视网膜病变有治疗作用。然而，非诺贝特可以在一次玻璃体内注射后迅速从眼睛中清除。在这里，我们的目标是开发非诺贝特PLGA微球(FeNO-MP)，具有高载药量和体外释放长达6个月的特点，适用于玻璃体内注射。首先，采用正交表试验设计进行处方优选。用选定的处方参数分别采用均质法和直接膜乳化法制备FeNO-MP。两种方法制备的FeNO-MP载药量均较高，体外释药时间均在140天以上。与均质法制备的多分散FeNO-MP不同，膜乳化法制备的FeNO-MP粒径分布均匀。通过控制膜的孔径，制备了1.5、8和16µm的FeNO-MP，发现较大的FeNO-MP具有更高的载药量、更持久的体外释药和较小的FeNO-MP更少的突释。综上所述，我们开发了具有高载药量和缓释特性的FeNO-MP，并阐明了改变颗粒大小对载药量和释放动力学有显著影响。采用膜乳化法制备出粒度分布均匀的FeNO-MP，有利于批间重复性。
Fenofibrate has shown therapeutic effects on diabetic retinopathy. However, fenofibrate can be rapidly cleared from the eye after a single intravitreal injection. Here, we aim to develop fenofibrate loaded PLGA microparticles (Feno-MP) with high drug loading and sustainedin vitrorelease up to 6 months suitable for intravitreal injection. First, orthogonal array experimental design was applied for formulation optimization. The selected formulation parameters were used to formulate Feno-MP using homogenization method and direct membrane emulsification method. Both methods generated Feno-MP with high drug loading and sustainedin vitrodrug release more than 140 days. Unlike the polydisperse Feno-MP prepared using homogenization method, membrane emulsification method generated Feno-MP with uniform size distribution. By controlling the membrane pore size, 1.5 µm, 8 µm and 16 µm Feno-MP were formulated and we found that larger Feno-MP demonstrated higher drug loading, more sustained drug releasein vitrowith less burst drug release than the smaller Feno-MP. In conclusion, we developed Feno-MP with high drug loading and sustained release profile, and elucidated that changing the particle size could have notable impacts on drug loading and release kinetics. Formulating Feno-MP with uniform size distribution by membrane emulsification method would benefit the batch-to-batch repeatability.