Encapsulação de anfotericina B em lipossomas como sistemas de entrega modificada do fármaco para aplicação endovenosa / Encapsulation of amphotericin B into liposomes as modified delivery systems of the drug for endovenous administration

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

08/04/2010

RESUMO

Fungal infections are among the most important causes of death among immunocompromised patients. Amphotericin B (AmB) is an antifungal polyene macrolide, representative of the group of chemotherapeutics which mechanism of action consists in change of membrane cell permeability. AmB is more damaging to fungal cells, but interacts with mammalian cell membrane too, causing severe side effects to patients on treatment. Selectivity and toxicity of AmB may be altered by its encapsulation into liposomes, consequently leading to higher therapeutic efficacy. The advantages liposomes as drug carriers are well documented, and account for the success of AmBisome®, an AmB liposomal formulation, marketed since 1989. Despite the advantages, liposomes are rapidly cleared from blood circulation. One of the most widely-used methods for enhancing the residence time of liposomes is the inclusion of pegylated phospholipids within its membrane surface (pegylated liposomes). This strategy modifies surface characteristics of liposome vesicles, making them sterically stabilized. Pegylated liposomes exhibit longer blood circulation time, which can result in accumulation of the encapsulated drug into specific and desired sites of drug action, and thus, increase its therapeutic efficacy. Pegylated liposomal formulations containing distearoylphosphatidylethanolamine(polyethyleneglycol), cholesterol, hydrogenated soy phosphatidilcholine (HSPC, formulation named Lip-PEGHSPC) and/or soy phosphatidilcholine (SPC, formulations named Lip-PEG50%SPC and Lip-PEGSPC) were prepared and characterized. The vesicles showed high quantities of AmB, zeta potential of around - 20 mV and diameters of 100 to 300 nm. The Lip-PEGHSPC formulation, to which AmB incorporation was confirmed through different behavior of free and liposomal AmB in spectrophotometric and spectrofluorimetric studies, exhibited good stability when maintained in suspension at 4 º C, and antifungal activity, in vitro, slightly superior to free AmB against C. parapsilosis, C. albicans e C. dublinensis, in a total of seven different tested strains. Therefore, Lip-PEGHSPC can be a viable, and possibly superior, alternative to currently available treatment using AmB.

ASSUNTO(S)

anfotericina b encapsulação lipossomas infecções fúngicas amphotericin b encapsulation liposomes fungal infections

ACESSO AO ARTIGO

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