Nanostructured lipid carriers for transdermal delivery of clotrimazole in cutaneous and subcutaneous mycoses: formulation, characterization and ex-vivo penetration tests.

LADETTO F; SALERNO C; ISLAN GA; CASTRO GR; GLISONI RJ; CUESTAS ML

Congreso; Reunión Anual de Sociedades de Biociencias. SAIC-SAFIS-ALACF.; 2024

Formulations based on nanostructured lipid carriers (NLCs) were developed for the transdermal delivery of clotrimazole (CLT) to treat cutaneous and subcutaneous mycoses. CLT, a widely used antifungal for topical treatments, has a high lipophilic character and poses challenges for absorption and bioavailability. Also, prolonged treatments and high doses often result in significant toxicity. Therefore, the use of lipid nanoparticles is proposed for its vehiculization and incorporation into hydroxypropylmethylcellulose (HPMC) gels to improve their application and controlled release.In this work, three formulations of NLCs obtained by emulsification/ultrasonication method were tested, using cetyl palmitate as solid lipid base and poloxamer 188 as surfactant. To increase the loading capacity and achieve therapeutic doses, three oils were used as structuring liquid lipids: geraniol, eugenol, and oleic acid. Stable suspensions of 130±15 nm NLCs were obtained, with high encapsulation efficiencies (>95%). An increase in the intrinsic solubility of the drug between 2,000 to 10,000 times was achieved. Finally, 2.0% HPMC was directly added to the NLC suspensions to produce homogeneous gels.Antifungal activity was demonstrated by agar diffusion assays against 13 clinical isolates associated with cutaneous and subcutaneous mycoses. In all cases, the activity was at least 2-times higher than that of free CLT. In vitro CLT release was controlled and sustained, following the Korsmeyer-Pepas model under sink conditions. Ex vivo penetration capacity was tested using the Franz cell model with pig ear skin. Unlike free CLT, which is tipically retained in the stratum corneum, geraniol- and eugenol-based NLCs delivered more than 50% of CLT to the epidermis, with the oleic acid-based one even reaching the dermis..Results depict the use of NLCs-containing gels as potential and promising transdermal delivery systems for treating cutaneous and subcutaneous mycoses.