经鼻给药α-细辛脑mPEG-PLA微粒的制备与体外释放研究

Preparation and release behaviour of mPEG-PLA α-asarone nanoparticles designed for nasal administration

以α-细辛脑为模型药物,单甲氧基聚乙二醇-聚乳酸共聚物(m PEG-PLA)为载体,采用快速膜乳化法制备经鼻给药载药微粒。所得微粒表面光滑、外观圆整,平均粒径为360 nm,多分散系数(PDI)为0.030,载药量及包封率分别为(11.5±0.045)%(n=3),(86.34±0.11)%(n=3)。X射线衍射和差示扫描量热结果均表明α-细辛脑是以无定形或分子态存在于m PEG-PLA载体中,而不同于简单的物理混合物。模拟人鼻腔内环境体外释放试验研究结果显示α-细辛脑原料药在102 h即释放接近94%,释放较快,符合一级动力学模型(R^2=0.981 9),而m PEG-PLA载药微粒释放只达54%,具有缓释作用,符合Riger-Peppas模型(R^2=0.967 9,n=0.630 2),为非Fick扩散,释放由药物的扩散和骨架溶蚀双重控制,为后续经鼻给药的体内药代动力学研究提供依据。

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer （mPEG-PLA） as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index （PDI） was 0. 030, average drug loading of （ 11.5 ± 0. 045 ） % （ n = 3 ） , and the encapsulation efficiency of （ 86. 34± 0. 11 ） % （ n = 3 ）. X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics （R2 = 0. 981 9 ）. mPEG-PLA drug-loading nanoparticles release only 54% , with slow release effect, in line with Riger-Peppas model （ R2 = 0. 967 9, n = 0.630 2 ） , for non-tick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.