Universidad Complutense de Madrid
E-Prints Complutense

New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp.

Impacto

Downloads

Downloads per month over past year

Ruiz, Helga K. and Serrano, Dolores R. and Dea Ayuela, María Auxiliadora and Bilbao Ramos, Pablo Estanislao and Bolás Fernández, Francisco and Torrado, Juan J. and Molero, Gloria (2014) New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp. International journal of pharmaceutics, 473 (1-2). pp. 148-57. ISSN 0378-5173

[img] PDF
Restringido a Repository staff only

1MB

Official URL: http://dx.doi.org/10.1016/j.ijpharm.2014.07.004



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Amphotericin B Cyclodextrin Topical formulations Antifungal activity Antileishmanial efficacy Biofilms
Subjects:Medical sciences > Pharmacy > Microbiology
ID Code:33644
Deposited On:26 Nov 2015 11:56
Last Modified:29 Nov 2015 15:17

Origin of downloads

Repository Staff Only: item control page