Optimizing efficacy of amphotericin B through nanomodification

Abstract

Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB-deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical effi cacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifi cations of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specifi c drug delivery.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

“…Pharmaceutical technology has been used to control pharmacokinetic properties, such as absorption, distribution, metabolism, and excretion and to improve the effi cacy and/or reduce the toxicity of drugs (24) . This review examines the development and deployment of technologies to improve the delivery of drugs for treating leishmaniasis.…”

Uses of Nanoparticles for Central Nervous System Imaging and Therapy

“…26 Nanoparticle-mediated selective drug delivery may allow a means to minimize delivery to unintended sites, potentially allowing larger doses of drug to be administered and with a greater percentage of drug reaching the target, thereby possibly lowering toxicity. 27 Many methods of selective delivery exist. In addition to targeting strategies using ligands on nanoparticle surfaces mentioned earlier, strategies have been devised for release of nanoparticle contents by using stimuli external to the body by means of a focused trigger, such as light (so-called "photodynamic therapy") or heat.…”

Nanomedicinal products: a survey on specific toxicity and side effects

“…Different formulations have been used to minimize nephrotoxicity including liposomal amphotericin B. Liposomal amphotericin B has proven to reduce the toxicities associated with the administration of the conventional deoxycholate formulation of amphotericin B and to have efficacy against various fungi. 30 The incorporation of amphotericin B into a liposome provides the toxicokinetic and mechanistic basis for the increased safety and tolerability. 30 Liposomal amphotericin B is intended for intravenous administration only, while conventional amphotericin B, is also available for oral administration.…”

“…30 The incorporation of amphotericin B into a liposome provides the toxicokinetic and mechanistic basis for the increased safety and tolerability. 30 Liposomal amphotericin B is intended for intravenous administration only, while conventional amphotericin B, is also available for oral administration. Table 5 presents an overview of the differences in type or frequency between the observed side effects of liposomal amphotericin B (as reported for the brand name AmBisome ® ) and conventional amphotericin B (as reported for the brand name Fungizone ® ).…”