In Vivo Safety and Efficacy of Chalcone-Loaded Microparticles with Modified Polymeric Matrix against Cutaneous Leishmaniasis

Abstract

Current chemotherapy of cutaneous leishmaniasis (CL) is based on repeated systemic or intralesional administration of drugs that often cause severe toxicity. Previously, we demonstrated the therapeutic potential of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) loaded with 8% of the nitrochalcone CH8 (CH8/PLGA) prepared by a conventional bench method. Aiming at an industrially scalable process and increased drug loading, new MPs were prepared by spray drying: CH8/PDE with PLGA matrix and CH8/PVDE with PLGA + polyvinylpyrrolidone (PVP) matrix, both with narrower size distribution and higher drug loading (18%) than CH8/PLGA. Animal studies were conducted to evaluate their clinical feasibility. Both MP types induced transient local swelling and inflammation, peaking at 1–2 days, following a single intralesional injection. Different from CH8/PDE that released 90% of the drug in the ear tissue in 60 days, CH8/PVDE achieved that in 30 days. The therapeutic efficacy of a single intralesional injection was evaluated in BALB/c mice infected with Leishmania (Leishmania) amazonensis and golden hamsters infected with L. (Viannia) braziliensis. CH8/PVDE promoted greater reduction in parasite burden than CH8/PDE or CH8/PLGA, measured at one month and two months after the treatment. Thus, addition of PVP to PLGA MP matrix accelerates drug release in vivo and increases its therapeutic effect against CL.

Nigella sativa loaded nanoparticles: A promising alternative treatment for murine schistosomiasis mansonai

“…(26) Experimentally in murine cutaneous leishmaniasis, polymeric nanoparticles have been used to deliver chalcone or amphotericin B intracellularly. (27) Metal nanoparticles (NPs), chitosan (CS), and liposomes are conjugated with a variety of drugs, including as praziquantel, chloroquine, amphotericin B, rifampicin, and albendazole, to treat schistosomiasis, malaria, visceral leishmaniasis (VL), and visceral larva migrans. (28) In Schistosoma mansonai, it was found that solid lipid nanoparticles coated with celecoxib effectively inhibited the various developmental stages of S. mansonai infection.…”