Journal Title
Title of Journal: Drug Deliv and Transl Res
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Abbravation: Drug Delivery and Translational Research
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Authors: Manisha B Chaudhari Preshita P Desai Pratikkumar A Patel Vandana B Patravale
Publish Date: 2015/12/28
Volume: 6, Issue: 4, Pages: 354-364
Abstract
Amphotericin B a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability Thus to alleviate the toxicity and to improve oral bioavailability an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B AmbiOnp was reported earlier by our group In this investigation we report the predominant formation of nontoxic superaggregated form of amphotericin B resulting from the probe sonicationassisted nanoprecipitation technique The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions Further in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7812 μg/mL attributed to controlled release of drug from nanoparticulate matrix In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 105fold with a Cmax of 110931 ± 10479 ng/mL at the end of 24 h which was comparable to Cmax of 141749 ± 8552 ng/mL achieved with that of marketed formulation Fungizone® given intravenously establishing efficacy of AmbiOnp In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies Further the formulations were found to be stable under refrigeration condition over a period of 3 monthsThe authors are grateful to the Life Care Innovation Pvt Ltd Delhi India ISP Technology Pvt Ltd India Degussa Pvt Ltd France and BASF Mumbai India for the generous gift samples of drug and excipients The authors are thankful to the University Grants Commission and Department of Science and Technology Government of India New Delhi India for the financial support extended for the research work
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