Development of a 17-DMAG-Loaded Carboxymethylcellulose Gel for In Vivo Treatment of Cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is a neglected tropical disease for which safer and more effective therapeutic options are urgently needed. Heat shock protein 90 (Hsp90) inhibitors have emerged as promising antileishmanial agents. Among geldanamycin derivatives, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) has previously demonstrated potent activity against Leishmania braziliensis. Here, we evaluated the therapeutic potential of a topical 17-DMAG formulation for CL. The compound exhibited low cytotoxicity toward human keratinocytes (HaCaT) and THP-1 macrophages cell-lines. A carboxymethylcellulose (CMC) hydrogel containing 17-DMAG showed physicochemical stability for up to 90 days at 4 and 25 °C, with diffusion-controlled drug release. In BALB/c mice infected with L. braziliensis, topical treatment induced mild and transient local inflammation, without systemic toxicity. Notably, the 0.10 mg/g formulation reduced lesion size by up to 47% and achieved 80% complete healing by week 3. These findings support topical 17-DMAG formulation as a safe, effective, and noninvasive therapeutic approach for experimental CL.