IngentaConnect Drug Delivery System of Anti-fungal and Parasitic Agents

Abstract:

The antifungal agents for systemic mycoses are only a few in number. Among them amphotericin-B is still the most widely used drug, but substantial side effects including nephrotoxicity limits its clinical usefulness. Efforts to lower the toxicity are synthesis of AMPH-B analogues such as AMPH-B esters and encapsulation in lipid vesicles in the forms of liposomal AMPH-B (AmBisome), amphotericin-B lipid complex (Abelcet), amphotericin-B colloidal dispersion (Amphocil) and intralipid AMPH-B. The newer formulations are effective against wide range of fungi, may be given in higher doses and nephrotoxicity is lowered. Although all of them showed comparable efficacies, a standard formulation is yet to be determined. In Japan, studies on efficacies of lipid nanosphere-encapsulated AMPH-B are in progress. Special drug career systems and dosage forms, such as nanoparticles and liposomes hold the promise of overcoming the pharmacokinetic limitations. Nanoparticles are stable, solid colloidal particles consisting of macromolecular material and vary in size. Nanoparticles represent an interesting carrier system for the specific enrichment in macrophage containing organs like liver and spleen. Injectable nanoparticle carriers have important potential applications as in sitespecific drug delivery. Modifications of liposomes in order to avoid uptake by RES, thus increase targetability has been attempted. A novel targetable liposome 34A-PEG-L modified with polyethylene glycol conjugated with MoAb, 34A specific to murine pulmonary epithelia has been evaluated in murine pulmonary aspergillosis. 34A-PEG-L-AmB showed higher tissue concentration and comparable efficacy than other AMPH-B formulations.

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