Permeability Characteristics of a New Antifungal Topical Amphotericin B Formulation with γ-Cyclodextrins

Abstract

Amphotericin B is a low soluble broad-spectrum antifungal agent. Cyclodextrins can be added to amphotericin formulations to enhance both their solubility and antifungal properties. Semisolid amphotericin formulations containing gamma cyclodextrin (AGCD) were prepared and compared with two reference formulations—one of them without any solubility enhancer (A) and the other with DMSO (ADMSO). Rheological, the permeability through hairless mouse skin and antifungal characteristics of the different formulations were evaluated. All three semisolid formulations show low thixotropy characteristics. ADMSO was the formulation with the least consistency, lowest viscosity, and greatest extensibility. The AGCD formulation had the opposite behavior and had both the greatest consistency and viscosity and the lowest extensibility. The lowest permeability was obtained with the reference A formulation while both AGCD and ADMSO had a similar permeability enhancement. According to the antimicrobial in vitro efficacy trials, the AGCD formulation showed 45–60% more activity than the reference A formulation. It can be concluded that γ-cyclodextrin is a useful excipient to improve the solubility, permeability, and antifungal activity of amphotericin B in semisolid topical formulations.

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

“…or oral routes, in terms of patient compliance and AmB therapeutic performance [182,183] despite the distinct physicochemical nature of AmB that compromises its skin permeation. Permeability enhancers such as dimethyl sulfoxide (DMSO) and cyclodextrins (CDs) have been added to AmB formulations to improve drug solubility [224]. Semisolid AmB topical formulations with added γ-CD showed shear-thinning and thixotropic behavior, improved skin permeability, and enhanced in vitro antifungal efficacy against Candida species and Sacharomyces cerevisiae compared with an AmB reference formulation containing no solubility enhancers [224].…”

“…Permeability enhancers such as dimethyl sulfoxide (DMSO) and cyclodextrins (CDs) have been added to AmB formulations to improve drug solubility [224]. Semisolid AmB topical formulations with added γ-CD showed shear-thinning and thixotropic behavior, improved skin permeability, and enhanced in vitro antifungal efficacy against Candida species and Sacharomyces cerevisiae compared with an AmB reference formulation containing no solubility enhancers [224]. Several studies on NE development for topical AmB delivery have shown their suitability for the treatment of skin fungal infections [180][181][182][183][184], based on the synergistic effects resulting from the combination of lipids and surfactants with the antifungal drug [181].…”

Development of Itraconazole-Loaded Polymeric Nanoparticle Dermal Gel for Enhanced Antifungal Efficacy

“…Ex vivo permeation studies were also performed in static Franz diffusion cells (as described in Section 2.5.2) using the male rat epidermis as a skin model; this was clamped between the donor and receptor compartments with the stratum corneum side facing up [20]. The rat skin was treated as described previously with permission obtained from the Ethics Commitment Jury [21]. The fur and lipids were removed from the skin.…”

Development of a Topical Amphotericin B and Bursera graveolens Essential Oil-Loaded Gel for the Treatment of Dermal Candidiasis

“…A topically administered AmB formulation can bypass these disadvantages from invasive administration techniques and thus permit treatment of localized infections in skin or mucous membranes [17]. However, the higher molecular weight (926 Da) and low solubility in water of AmB could limit its passage through the skin [18]. These complications could be circumvented by incorporating excipients with permeationenhancing properties that promote the penetration of drugs through the stratum corneum (SC) and its distribution to the epidermis and dermis [19].…”