Antileishmanial and Immunomodulatory Activity of Paclitaxel and Docetaxel Combined with Miltefosine and Paromomycin

A wide range of Leishmania species, transmitted by phlebotomine, cause a group of diseases known as leishmaniasis, which present diverse clinical manifestations. Leishmaniasis has a high impact on the most vulnerable communities, primarily affecting people suffering from malnutrition or living in poor housing conditions. Due to leishmaniasis are strongly associated with poverty the access to treatment is often limited. Besides, high drug toxicity and therapeutic failure, related to the emergence of drug resistance, remain major challenges associated with currently available treatments. Therefore, there is a need for developing new therapeutic approaches safer and more effective. Drug combinations and drug repurposing are two strategies currently used in the development of new treatments targeting multiple diseases. The combination of drugs with different mechanisms of action can minimize the emergence of resistance and allow drug dosage reduction, increasing the likelihood of successful drug repurposing. The research evaluated the leishmanicidal effects of combining antitumoral agents (paclitaxel and docetaxel) with standard drugs (miltefosine and paromomycin). Results demonstrated synergistic effects at higher doses. Furthermore, the antitumoral compounds boosted the host immune response by promoting macrophage polarization toward the M1 phenotype, which is essential for parasite control. These findings highlight a promising therapeutic approach that could improve treatment efficacy and reduce resistance.