title: Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.
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 sonication-assisted 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 7.812 μg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 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 months.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, Maharashtra, India.
authors.forename: Manisha B
authors.initials: MB
authors.lastname: Chaudhari
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, Maharashtra, India.
authors.forename: Preshita P
authors.initials: PP
authors.lastname: Desai
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, Maharashtra, India.
authors.forename: Pratikkumar A
authors.initials: PA
authors.lastname: Patel
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, Maharashtra, India. vbp_muict@yahoo.co.in.
authors.forename: Vandana B
authors.initials: VB
authors.lastname: Patravale
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D000666:Amphotericin B
keywords: Aggregation state; AmbiOnp; Nephrotoxicity; Oral bioavailability; Solid lipid nanoparticles