常规脂质体与聚乙二醇化脂质体的混合制剂作为一种新型药物递送策略用于改善内脏利什曼病的治疗

Mixed formulation of conventional and pegylated liposomes as a novel drug delivery strategy for improved treatment of visceral leishmaniasis.

作者信息

Azevedo Erly G, Ribeiro Raul R, da Silva Sydnei M, Ferreira Cláudio S, de Souza Ligia E, Ferreira Adriel Af, de Oliveira E Castro Renata A, Demicheli Cynthia, Rezende Simone A, Frézard Frédéric

机构信息

Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Fisiologia e Biofísica , Av. Antônio Carlos 6627, Pampulha, 31270-901 Belo Horizonte, Minas Gerais , Brazil +55 31 34092940 ; +55 31 34092924 ;

出版信息

Expert Opin Drug Deliv. 2014 Oct;11(10):1551-60. doi: 10.1517/17425247.2014.932347. Epub 2014 Jun 25.

Abstract

OBJECTIVE

Test the hypothesis that pegylated meglumine antimoniate-containing liposomes (LMA) and their mixture with non-pegylated (conventional) LMA may be more effective than conventional LMA against visceral leishmaniasis (VL), because of wider drug distribution among different mononuclear phagocyte system (MPS) tissues.

METHODS

Sb was determined in the blood and MPS tissues after administration of pegylated or conventional LMA intravenously to mongrel dogs naturally infected with Leishmania infantum and Swiss mice. Pegylated and conventional LMA as well as their mixture were evaluated for their antileishmanial efficacy in BALB/c infected with L. infantum through determination of parasite load in liver, spleen and bone marrow.

RESULTS

An improved targeting of Sb to the bone marrow of dogs was clearly evidenced, as an important impact of pegylation. In accordance with this data, pegylated LMA significantly reduced parasite load in bone marrow of infected mice, in contrast to conventional LMA. The mixed formulation of conventional and pegylated LMA promoted parasite suppression to a higher extent in both spleen and bone marrow, compared to pegylated or conventional LMA.

CONCLUSIONS

The present work establishes for the first time the potential of mixed formulations of conventional and pegylated liposomes as a drug delivery strategy for improved treatment of VL.

摘要

目的

验证以下假说:聚乙二醇化含葡甲胺锑酸盐脂质体(LMA)及其与非聚乙二醇化(传统)LMA的混合物,相较于传统LMA,对内脏利什曼病(VL)可能更有效,因为药物在不同单核吞噬细胞系统(MPS)组织中的分布更广泛。

方法

对自然感染婴儿利什曼原虫的杂种犬和瑞士小鼠静脉注射聚乙二醇化或传统LMA后,测定血液和MPS组织中的锑含量。通过测定感染婴儿利什曼原虫的BALB/c小鼠肝脏、脾脏和骨髓中的寄生虫载量,评估聚乙二醇化和传统LMA及其混合物的抗利什曼原虫疗效。

结果

聚乙二醇化的一个重要影响是,明显证明了锑在犬骨髓中的靶向性得到改善。根据这些数据,与传统LMA相比,聚乙二醇化LMA显著降低了感染小鼠骨髓中的寄生虫载量。与聚乙二醇化或传统LMA相比,传统LMA与聚乙二醇化LMA的混合制剂在脾脏和骨髓中对寄生虫的抑制作用更强。

结论

本研究首次证实了传统脂质体与聚乙二醇化脂质体的混合制剂作为一种药物递送策略,在改善VL治疗方面的潜力。

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