Document Type : Original Articles
Authors
1
Department of Parasitology and Mycology Islamic Azad University, Mashhad, Iran
2
Toxoplasmosis Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
3
Department of Basic Sciences, Faculty of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Science, Gonabad, Iran
4
Bachelor Student of Chemistry, Leibniz University, Hannover, Germany
5
Innovative Medical Research Centre, MMS.C., Islamic Azad University, Mashhad, Iran.
10.22092/ari.2025.370355.3783
Abstract
ABSTRACT
Cutaneous leishmaniasis (CL) remains a significant global health challenge, particularly in endemic regions. Current first-line therapies, such as Glucantime® (meglumine antimoniate), are frequently limited by systemic toxicity, demanding administration routes, and variable clinical efficacy, underscoring the urgent need for improved treatment strategies. This study investigated a alternative approach to overcome these limitations: nanoparticle-enhanced delivery of Glucantime utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) carriers designed to improve therapeutic outcomes and reduce adverse effects. Glucantime was successfully encapsulated within ~200 nm PLGA nanoparticles (PLGA-Glu NPs) using a double-emulsion (W/O/W) solvent evaporation technique. Therapeutic efficacy was comprehensively evaluated in a stringent Leishmania major-infected BALB/c mice (n=6 per group). Groups received subcutaneous injections every 3 days for 4 weeks as follows: 1) PBS (negative control), 2) Free Glucantime (10 mg/kg), 3) Blank PLGA NPs (vehicle control), 4) Low-dose PLGA-Glu NPs (100 pg), and 5) High-dose PLGA-Glu NPs (300 pg). PLGA-Glu NPs demonstrated potent and significant immunomodulatory effects. levels of cytokine IL-10 were markedly suppressed in mice treated with the nanoformulations (p<0.01). Subsequent splenocyte analysis confirmed a profound reduction in IL-10 secretion (p<0.001) and revealed robust Th1-promoting activity, evidenced by significantly elevated production of IL-2 (p<0.05). Most notably, treatment with high-dose PLGA-Glu NPs achieved near-complete clinical resolution of cutaneous lesions, supported histologically by minimal residual inflammation and tissue architecture restoration. Furthermore, antigen-specific lymphoproliferative responses were significantly attenuated in PLGA-Glu NP-treated mice (p<0.001). In conclusion, these compelling findings position PLGA nanoencapsulation of Glucantime as alternative therapeutic strategy for cutaneous leishmaniasis, though future studies must prioritize comprehensive toxicological profiling, and long-term efficacy assessment in chronic infection models to facilitate clinical translation.
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