title: Development of oil-in-water microemulsions for the oral delivery of amphotericin B.
abstract: Amphotericin B (AmB) is a very efficient drug against serious diseases such as leishmaniasis and systemic fungal infections. However, its oral bioavailability is limited due to its poor solubility in water. Nevertheless, it is marketed as high-cost lipid parenteral formulations that may induce serious infusion-related side effects. In this study, oil-in-water (O/W) microemulsions (MEs) were developed and characterized with a view to their use as solubility enhancers and oral delivery systems for AmB. Therefore, different nonionic surfactants from the Tween(®) and Span(®) series were tested for their solubilization capacity in combination with several oils. Based on pseudoternary phase diagrams, AmB-loaded MEs with mean droplet sizes about 120 nm were successfully produced. They were able to improve the drug solubility up to 1000-fold. Rheological studies showed the MEs to be low-viscosity formulations with Newtonian behavior. Circular dichroism and absorption spectra revealed that part of the AmB in the MEs was aggregated as an AmB reservoir carrier. Cytotoxicity studies revealed limited toxicity to macrophage-like cells that may allow the formulations to be considered as suitable carriers for AmB.
authors.affiliation: Universidade Federal do Rio Grande do Norte, Faculdade Farmácia, Laboratório de Sistemas Dispersos (LASID), Rua Gal. Cordeiro de Farias, S/N, Petrópolis, Zip Code 59010-180 Natal, RN, Brazil. acariliasilva@gmail.com
authors.forename: Acarília Eduardo
authors.initials: AE
authors.lastname: Silva
authors.forename: Gillian
authors.initials: G
authors.lastname: Barratt
authors.forename: Monique
authors.initials: M
authors.lastname: Chéron
authors.forename: E Sócrates T
authors.initials: ES
authors.lastname: Egito
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004655:Emulsions; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D012212:Rheology; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; D014867:Water; D000666:Amphotericin B
keywords: Amphotericin B; In vitro toxicity; Lipids; Microemulsions; Rheology; Surfactants