Ramos Guilherme S, Vallejos Virgínia M R, Borges Gabriel S M, Almeida Raquel M, Alves Izabela M, Aguiar Marta M G, Fernandes Christian, Guimarães Pedro P G, Fujiwara Ricardo T, Loiseau Philippe M, Ferreira Lucas A M, Frézard Frédéric
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Pharmaceutics. 2022 May 5;14(5):989. doi: 10.3390/pharmaceutics14050989.
Liposomal amphotericin B (AmB) or AmBisome is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome in -infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100-130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.
脂质体两性霉素B（AmB）或两性霉素B脂质体是治疗内脏利什曼病（VL）最有效且安全的药物，但在皮肤利什曼病（CL）和HIV/VL合并感染中其临床疗效有限。本研究的目的是开发一种聚乙二醇化脂质体包裹的AmB制剂，并在CL小鼠模型中比较其与两性霉素B脂质体的疗效。对常规脂质体和聚乙二醇化脂质体包裹的AmB制剂的粒径、形态、药物包封率和聚集状态进行了表征。将这些制剂与感染的BALB/c小鼠体内的两性霉素B脂质体比较，观察它们对病灶大小增长和寄生虫负荷的影响。常规制剂和聚乙二醇化制剂均显示出直径为100 - 130 nm且多分散性低的囊泡，以非聚集形式包封了超过95%的AmB。在CL小鼠模型中进行肠胃外给药后，与对照组相比，聚乙二醇化AmB制剂显著减小了病灶大小增长并降低了寄生虫负荷，而常规脂质体AmB则不然。聚乙二醇化AmB制剂采用2天给药方案经口服给药时也有效。本研究首次报道聚乙二醇化脂质体AmB可通过肠胃外和口服途径改善实验性皮肤利什曼病的治疗效果。
