title: Amphotericin B-loaded nanocarriers for topical treatment of cutaneous leishmaniasis: development, characterization, and in vitro skin permeation studies.
abstract: Topical treatment of cutaneous leishmaniasis represents an exciting alternative for reducing toxicity associated with parenteral administration of conventional amphotericin B. This work aims to develop and to characterize amphotericin B-loaded new carriers and to investigate their potential for topical delivery by conducting permeation studies with pig ear skin in comparison with marketed formulations. Among other formulations, nanoemulsions were developed and characterized for size, encapsulation efficiency, and zeta potential. To mimic use conditions in topical therapy of cutaneous leishmaniasis, in vitro skin permeation experiments were conducted using a damaged skin model. High encapsulation efficiency (95%) and low particle size (239 nm) were obtained for amphotericin B-loaded nanoemulsion by employing an ion pairing between the drug and stearylamine. Amphotericin B permeation after 24 h across the dermal membrane was low, regardless of the type of formulation tested. In contrast, amphotericin B penetration into dermal membranes (microg/cm2) from solution (control), aqueous Amphocil, hydroalcoholic Amphocil, Fungizone, mixture Fungizone-Lipofundin, and NE was 17.5 +/- 4, 15.2 +/- 3, 9.6 +/- 3, 3.5 +/- 1, 1.7 +/- 0.3, and 1.1 +/- 0.1, respectively. Amphocil provided the best results, highlighted by its high improvement of dermal penetration of amphotericin B.
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Cristiane Moraes
authors.initials: CM
authors.lastname: Santos
authors.forename: Renata Barbosa
authors.initials: RB
authors.lastname: de Oliveira
authors.forename: Valquíria Teresa
authors.initials: VT
authors.lastname: Arantes
authors.forename: Leila Rodrigues
authors.initials: LR
authors.lastname: Caldeira
authors.forename: Monica Cristina
authors.initials: MC
authors.lastname: de Oliveira
authors.forename: Eryvaldo Sócrates Tabosa
authors.initials: ES
authors.lastname: Egito
authors.forename: Lucas Antônio Miranda
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D000279:Administration, Cutaneous; D000588:Amines / Q000737:chemistry; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D000588:Amines; D000981:Antiprotozoal Agents; D004655:Emulsions; D000666:Amphotericin B; C009317:stearylamine