NANOSTRUCTURED LIPID CARRIERS FOR TRANSDERMAL DELIVERY OF CLOTRIMAZOLE IN CUTANEOUS AND SUBCUTANEOUS MYCOSES: FORMULATION, CHARACTERIZATION AND EX VIVO PENETRATION TESTS

LADETTO, MARÍA FLORENCIA; SALERNO, CLAUDIA; ISLAN, GERMAN; CASTRO, GUILLERMO R.; GILSONI, ROMINA; CUESTAS, MARÍA LUJÁN

Buenos Aires

Encuentro; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2024

Nanostructured lipid carriers (NLC) were developed to control clotrimazole (CLT) release and enhance its transdermal delivery for treating cutaneous and subcutaneous mycoses. CLT, a widely used antifungal for topical treatments, presents challenges due to its lipophilicity, which limits solubility, absorption and bioavailability, whereas high-dose and prolonged treatments often lead to toxicity. To address these issues, CLT was incorporated into NLCs and further formulated into hydroxypropylmethylcellulose (HPMC) gels. Three NLC formulations were synthesized via emulsification/ultrasonication method, using cetyl-palmitate as solid lipid and poloxamer 188 as surfactant. Geraniole, eugenole, and oleic acid were selected as liquid lipids in order to enhance loading capacity, achieve therapeutic concentrations and improve therapeutic efectiveness. The resulting NLCs, with an average size of 130±15 nm and encapsulation efficiencies exceeding 95%, significantly improved the intrinsic solubility of CLT by 2,000 to 10,000 times. 2% HPMC was directly incorporated into the NLC suspensions to produce homogeneous gels. The antifungal efficacy of these formulations was confirmed through agar diffusion assays against 13 clinical isolates, showing at least a two-fold increase in activity compared to free CLT. In vitro release studies demonstrated controlled and sustained drug release, fitting the Korsmeyer-Peppas model under sink conditions. Ex vivo studies using the Franz cell model with pig ear skin revealed that NLC formulations significantly enhanced CLT penetration with over 50% of the drug reaching the epidermis and, in the case of oleic acid-based NLCs, even the dermis, with no penetration to receptor fluid. These findings suggest that NLC-based gels represent a promising approach for the transdermal treatment of cutaneous and subcutaneous mycoses.