RT Journal Article
T1 New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp.
A1 Ruiz, Helga K.
A1 Serrano López, Dolores Remedios
A1 Dea Ayuela, María Auxiliadora
A1 Bilbao Ramos, Pablo Estanislao
A1 Bolas Fernández, Francisco
A1 Torrado Durán, Juan José
A1 Molero, Gloria
AB Amphotericin B (AmB) has a broad antifungal and leishmanicidal activity with low incidence of clinical resistance. Its parenteral administration has high risk of nephrotoxicity that limits its use. In order to treat cutaneous infections, AmB topical administration is a safer therapy because of the low systemic absorption of the drug across mucous membranes. Moreover, in some developing countries both fungal topical infections and cutaneous leishmaniasis are an important health problem. The aim of this work is to formulate a topical amphotericin preparation and test its in vitro antifungal (against 11 different fungal species) and antileishmanial activity. γ-Cyclodextrin (γ-CD) was chosen to solubilise AmB. Furthermore, γ-CD has shown a synergistic effect on membrane destabilization with AmB. Topical novel formulations based on AmB-CD complex have exhibited greater antifungal activity (48%, 28% and 60% higher) when compared to AmB Neo-Sensitabs(®) disks, AmB dissolved in dimethyl sulfoxide (DMSO) and Clotrimazole(®) cream, respectively. Furthermore, AmB-CD methyl cellulose gel has shown significantly higher inhibition activity on biofilm formation, larger penetration through yeast biofilms and higher fungicidal activity on biofilm cells compared to AmB dissolved in DMSO. In addition, AmB-CD gel exhibited both high in vitro leishmanicidal efficacy with wider therapeutic index (between 2 and 8-fold higher than AmB deoxycholate depending on Leishmania spp.) and also in vivo activity in an experimental model of cutaneous leishmaniasis. These results illustrate the feasibility of a topical AmB formulation easy to prepare, physicochemically stable over 6 months, safe and effective against diverse fungal and parasitic cutaneous infections.
PB Elsevier
SN 0378-5173
YR 2014
FD 2014-07-03
LK https://hdl.handle.net/20.500.14352/34924
UL https://hdl.handle.net/20.500.14352/34924
LA eng
NO Ruiz, H. K., Serrano López, D. R., Dea Ayuela, M. A. et al. «New Amphotericin B-Gamma Cyclodextrin Formulation for Topical Use with Synergistic Activity against Diverse Fungal Species and Leishmania Spp». International Journal of Pharmaceutics, vol. 473, n.o 1-2, octubre de 2014, pp. 148-57. DOI.org (Crossref), https://doi.org/10.1016/j.ijpharm.2014.07.004.
NO Ministerio de Economía, Comercio y Empresa (España)
DS Docta Complutense
RD 11 abr 2025