Topical meglumine antimoniate gel for cutaneous leishmaniasis: formulation, evaluation, and in silico insights Sosa, Lilian Espinoza, Lupe Carolina Pujol, Alba Correa-Basurto, José Méndez Luna, David Sarango Granda, Paulo Berenguer, Diana Riera, Cristina Clares Naveros, Beatriz Calpena, Ana Cristina Prohens, Rafel Silva-Abreu, Marcelle Meglumine antimoniate Skin Leishmania infantum Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/gels11080601/s1, Figure S1: DSC thermogram of pure meglumine antimoniate; Figure S2: DSC thermogram of pure pluronic acid; Figure S3: DSC thermogram of the mixture of the components of the formulation in the original proportion. Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 μg/g/cm2 of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC50 for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 μg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. 2025-11-04T07:52:41Z 2025-11-04T07:52:41Z 2025-08-01 journal article Sosa, L.; Espinoza, L.C.; Pujol, A.; Correa-Basurto, J.; Méndez-Luna, D.; Sarango-Granda, P.; Berenguer, D.; Riera, C.; Clares- Naveros, B.; Calpena, A.C.; et al. Topical Meglumine Antimoniate Gel for Cutaneous Leishmaniasis: Formulation, Evaluation, and In Silico Insights. Gels 2025, 11, 601. https://doi.org/10.3390/gels11080601 https://hdl.handle.net/10481/107715 10.3390/gels11080601 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License MDPI