Synthesis, characterization, and comparative evaluation of hydroxychloroquine and its niosomal nanoformulation: anti-leishmanial, cytotoxicity, and immunomodulatory effects in photodynamic therapy

Leishmaniasis, caused by the Leishmania parasites, is a significant global health issue with treatment challenges, particularly in endemic regions such as Iran. Current therapies, such as Meglumine antimoniate (MA), Amphotericin B, and Miltefosine, have limitations like high costs and side effects, necessitating innovative approaches. This study evaluates hydroxychloroquine (HC), an antimalarial drug with immunomodulatory properties, against Leishmania tropica (L. tropica), the causative agent of cutaneous leishmaniasis. We explored photodynamic therapy (PDT) and encapsulated HC in niosomal delivery systems with CdS/MIL-125(Ti) nanocomposites (FN) to enhance drug targeting. PDT utilizes these materials to produce reactive oxygen species, targeting cells effectively. Hydroxychloroquine-CdS/MIL-125(Ti)-loaded niosomes (NHC) were synthesized, characterized, and their in vitro anti-leishmanial activities were assessed alongside HC and MA. Results showed that NHC significantly improved anti-leishmanial effects, reducing viability in both promastigote and amastigote forms. Additionally, HC demonstrated favorable interactions with key proteins through molecular docking, modulated cytokine production, and induced apoptosis in infected macrophages. PDT further boosted the efficacy of both HC and NHC. This study indicates that niosomal encapsulation of HC enhances its delivery and efficacy, highlighting the potential for combination therapies in treating L. tropica. Further, in vivo studies are recommended to confirm these findings.