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Pharm Res. 2009 Jun;26(6):1324-31. doi: 10.1007/s11095-009-9841-2. Epub 2009 Feb 13.

Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone.

Author information

1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.

Abstract

PURPOSE:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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 approximately 800% as compared to Fungizone.

CONCLUSION:

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.

PMID:
19214716
DOI:
10.1007/s11095-009-9841-2
[Indexed for MEDLINE]

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