Enhanced Nanogel Formulation Combining the Natural Photosensitizer Curcumin and Pectis brevipedunculata (Asteraceae) Essential Oil for Synergistic Daylight Photodynamic Therapy in Leishmaniasis Treatment

<b>Background/Objectives</b>: Neglected tropical diseases (NTDs), such as leishmaniasis, remain a global health challenge due to limited therapeutic options and rising drug resistance. In this study, we developed an advanced nanogel formulation incorporating curcumin (CUR) and <i>Pectis brevipedunculata</i> essential oil (EO<i>Pb</i>) within an F127/Carbopol 974P matrix to enhance bioavailability and therapeutic efficacy against <i>Leishmania (Leishmania) amazonensis</i> (<i>LLa</i>) promastigotes. <b>Methods</b>: The chemical profile of EO<i>Pb</i> was determined through GC-MS and NMR analyses, confirming the presence of key bioactive monoterpenes such as neral, geranial, α-pinene, and limonene. The nanogel formulation (nG<i>P</i>C) was optimized to ensure thermosensitivity, and stability, exhibiting a sol-gel transition at physiological temperatures. Rheological analysis revealed that nG<i>P</i>C exhibited Newtonian behavior at 5 °C, transitioning to shear-thinning and thixotropic characteristics at 25 and 32 °C, respectively. This behavior facilitates its application and controlled drug release, making it ideal for topical formulations. Dynamic light scattering (DLS) analysis demonstrated that nG<i>P</i>C maintained a stable nanoscale structure with hydrodynamic radius below 300 nm, while Fourier-transform infrared spectroscopy (FTIR) confirmed strong molecular interactions between EO<i>Pb</i>, CUR, and the polymer matrix. Biological assays demonstrated that nG<i>P</i>C significantly enhanced anti-promastigote activity compared to free CUR and OE<i>P</i>b. <b>Results</b>: At the highest tested concentration (50 μg/mL EO<i>Pb</i> and 17.5 μg/mL CUR) nG<i>P</i>C induced over 88% mortality in <i>LLa</i> promastigotes across 24, 48, and 72 h, indicating sustained efficacy. Even at lower concentrations, nG<i>P</i>C retained dose-dependent activity, suggesting a synergistic effect between CUR and EO<i>Pb</i>. These findings highlight the potential of nG<i>P</i>C as an innovative nanocarrier for daylight photodynamic therapy (dPDT) in the treatment of leishmaniasis. Future studies will investigate the underlying mechanisms of this synergism and explore the potential application of photodynamic therapy (PDT) to further enhance therapeutic outcomes.