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

J.L. Italia, M.M. Yahya, D. Singh, M.N.V. Ravi Kumar

Research output: Contribution to journalArticle

98 Citations (Scopus)

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.
LanguageEnglish
Pages1324-1331
Number of pages7
JournalPharmaceutical Research
Volume26
Issue number6
DOIs
Publication statusPublished - 2009

Fingerprint

Amphotericin B
Nanoparticles
Biological Availability
Dialysis membranes
Polyglactin 910
Leishmaniasis
Mycoses
Antifungal Agents
Hemolysis
Particle Size
Pharmaceutical Preparations
Communicable Diseases
Rats
Dialysis
Blood
Erythrocytes
Cells

Keywords

  • amphotericin B
  • bioavailability
  • biodegradable
  • nephrotoxicity
  • oral delivery
  • pharmacology

Cite this

Italia, J.L. ; Yahya, M.M. ; Singh, D. ; Kumar, M.N.V. Ravi. / Biodegradable nanoparticles improve oral bioavailability of Amphotericin B and shows reduced nephrotoxicity against intravenous Fungizone®. In: Pharmaceutical Research. 2009 ; Vol. 26, No. 6. pp. 1324-1331.
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Biodegradable nanoparticles improve oral bioavailability of Amphotericin B and shows reduced nephrotoxicity against intravenous Fungizone®. / Italia, J.L.; Yahya, M.M.; Singh, D.; Kumar, M.N.V. Ravi.

In: Pharmaceutical Research, Vol. 26, No. 6, 2009, p. 1324-1331.

Research output: Contribution to journalArticle

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AU - Italia, J.L.

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