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Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®

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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 ∼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.

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Acknowledgement

Authors acknowledge financial support from Department of Science and Technology (DST), Government of India. M. M. Yahya is grateful to NIPER for providing MS fellowship. Dr. V. Beniwal is acknowledged for AFM imaging.

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Authors and Affiliations

  1. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK

    J. L. Italia & M. N. V. Ravi Kumar

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, 160062, Punjab, India

    M. M. Yahya & D. Singh

Authors
  1. J. L. Italia
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  2. M. M. Yahya
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  3. D. Singh
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  4. M. N. V. Ravi Kumar
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Correspondence to M. N. V. Ravi Kumar.

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Italia, J.L., Yahya, M.M., Singh, D. et al. Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®. Pharm Res 26, 1324–1331 (2009). https://doi.org/10.1007/s11095-009-9841-2

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  • DOI: https://doi.org/10.1007/s11095-009-9841-2

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