title: Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B.
abstract: Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Serafim
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Ferreira
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; CBIOS-Universidade Lusófona's Research Center for Biosciences and HealthTechnologies, Campo Grande 376, 1749-024 Lisbon, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Rijo
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Lídia
authors.initials: L
authors.lastname: Pinheiro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: cfaustino@ff.ulisboa.pt.
authors.forename: Célia
authors.initials: C
authors.lastname: Faustino
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Calado
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia-Rio
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000737:chemistry*; D003840:Deoxycholic Acid / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008826:Microbial Sensitivity Tests; D012212:Rheology; D020358:Sodium Cholate / Q000737:chemistry*; D012995:Solubility; D013500:Surface Tension; D014783:Viscosity
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008823:Micelles; D003840:Deoxycholic Acid; D000666:Amphotericin B; D003545:Cysteine; D020358:Sodium Cholate
keywords: Amphotericin B; Amphotericin B (PubChem CID: 5280965); Bile salts; Lipoamino acid; Mixed micelles; Sodium cholate (PubChem CID: 23668194); Sodium deoxycholate (PubChem CID: 23668196); l-Cystine (PubChem CID: 67678)