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Biodegradable nanoparticles improve oral bioavailability of Amphotericin B and shows reduced nephrotoxicity against intravenous Fungizone®

Italia, J.L. and Yahya, M.M. and Singh, D. and Kumar, M.N.V. Ravi (2009) Biodegradable nanoparticles improve oral bioavailability of Amphotericin B and shows reduced nephrotoxicity against intravenous Fungizone®. Pharmaceutical Research, 26 (6). pp. 1324-1331. ISSN 0724-8741

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Abstract

Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it. The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats. The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6 ± 2.9 nm with 34.5 ± 2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone®. The relative oral bioavailability of the AMB-NP was found to be ∼800% as compared to Fungizone®. Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.

Item type: Article
ID code: 13152
Keywords: amphotericin B, bioavailability, biodegradable, nephrotoxicity, oral delivery, pharmacology, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Organic Chemistry, Pharmaceutical Science, Molecular Medicine, Biotechnology, Pharmacology, Pharmacology (medical)
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Ms Ann Barker-Myles
    Date Deposited: 05 Oct 2009 16:09
    Last modified: 04 Sep 2014 23:18
    URI: http://strathprints.strath.ac.uk/id/eprint/13152

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