Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar (Mohali), Punjab-160062, India.
Mol Pharm. 2012 Sep 4;9(9):2542-53. doi: 10.1021/mp300320d. Epub 2012 Aug 14.
Amphotericin B (AmB) loaded polymer lipid hybrid nanoparticles (AmB-PLNs) comprised of lecithin (anionic lipid) and gelatin (Type A, cationic below its isoelectric point 7.0-9.0) were prepared by a two-step desolvation method to improve the oral bioavailability of AmB. The optimized AmB-PLNs were found to have particle size 253 ± 8 nm, polydispersity index (PDI) 0.274 ± 0.008, and entrapment efficiency 50.61 ± 2.20% at 6% w/w of initial theoretical drug loading. Scanning electron microscopy (SEM) revealed spherical shaped nanoparticles whereas confocal laser scanning electron microscopy (CLSM) and fluorescent resonance energy transfer (FRET) analysis confirmed the orientation of the lecithin (located in the core) and gelatin (exterior coat) within the system. The developed formulation exhibited a sustained drug release profile with a release pattern best fitted to Higuchi kinetics. Experiments on Caco-2 cell lines revealed a 5.89-fold increase in the intestinal permeability of AmB-PLNs whereas in vivo pharmacokinetic studies exhibited a 4.69-fold increase in the oral bioavailability upon incorporation of AmB into PLNs as compared to that of free drug. The developed formulation showed significantly lesser hemolytic toxicity as compared to the free drug, Fungizone (micellar solution of AmB) and Fungisome (liposomal formulation of AmB). Furthermore, blood urea nitrogen (BUN) and plasma creatinine levels, indicative of nephrotoxicity, were also found to be significantly lesser for developed PLN formulation as compared to free drug and Fungizone while comparable to that of Fungisome. The histopathology of the kidney tissues further confirmed the absence of any changes in the morphology of the renal tubules.
两性霉素 B（AmB）负载聚合物脂质杂化纳米粒（AmB-PLNs）由卵磷脂（阴离子脂质）和明胶（低于等电点 7.0-9.0 的阳离子）组成，采用两步去溶剂化法制备，以提高 AmB 的口服生物利用度。优化的 AmB-PLNs 的粒径为 253±8nm，多分散指数（PDI）为 0.274±0.008，在 6%w/w 的初始理论药物载量下，包封效率为 50.61±2.20%。扫描电子显微镜（SEM）显示出球形纳米粒，而共聚焦激光扫描电子显微镜（CLSM）和荧光共振能量转移（FRET）分析证实了卵磷脂（位于核心）和明胶（外涂层）在系统中的取向。所开发的制剂表现出持续的药物释放曲线，释放模式最佳拟合 Higuchi 动力学。在 Caco-2 细胞系上的实验表明，AmB-PLNs 的肠道通透性增加了 5.89 倍，而体内药代动力学研究表明，与游离药物相比，将 AmB 纳入 PLNs 可使口服生物利用度增加 4.69 倍。与游离药物、Fungizone（AmB 的胶束溶液）和 Fungisome（AmB 的脂质体制剂）相比，所开发的制剂的溶血毒性明显降低。此外，血尿素氮（BUN）和血浆肌酐水平，表明肾毒性，也发现显著低于开发的 PLN 制剂，比游离药物和 Fungizone 低，但与 Fungisome 相当。肾组织的组织病理学进一步证实了肾小管形态没有任何变化。
