Italia J L, Yahya M M, Singh D, Ravi Kumar M N V
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.
Pharm Res. 2009 Jun;26(6):1324-31. doi: 10.1007/s11095-009-9841-2. Epub 2009 Feb 13.
Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it.
The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats.
The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6 +/- 2.9 nm with 34.5 +/- 2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone. The relative oral bioavailability of the AMB-NP was found to be approximately 800% as compared to Fungizone.
Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.
两性霉素B（AMB）是一种有效的抗真菌和抗利什曼原虫药物，但其口服生物利用度低（0.3%）且具有严重的肾毒性。将其包裹于聚（丙交酯-乙交酯）（PLGA）纳米粒中，以提高口服生物利用度并将与之相关的不良反应降至最低。
采用纳米沉淀法，以维生素E-TPGS为稳定剂制备AMB纳米粒（AMB-NP）。采用膜透析法进行体外释放实验。通过与红细胞（RBCs）孵育评估AMB-NP的体外溶血活性。在大鼠中评估AMB-NP的急性肾毒性特征和口服生物利用度。
制备的AMB-NP制剂含有单分散颗粒，粒径范围为165.6±2.9nm，初始载药量为10%w/w时包封率为34.5±2.1%。AMB-NP制剂呈现双相药物释放，即初始快速释放后持续释放。与两性霉素B注射剂相比，AMB-NP制剂的溶血和肾毒性较低。与两性霉素B注射剂相比，AMB-NP的相对口服生物利用度约为800%。
总之，这些结果为口服AMB-NP治疗系统性真菌感染和利什曼病提供了可能性，这可能会彻底改变传染病的治疗方式。
