In Vivo Safety and Efficacy of Chalcone-Loaded Microparticles with Modified Polymeric Matrix against Cutaneous Leishmaniasis
Ariane de J. Sousa-Batista,
Natalia Arruda-Costa,
Wallace Pacienza-Lima,
Felipe Carvalho-Gondim,
Rosiane F. Santos,
Silvia A. G. Da-Silva,
Maria Inês Ré,
Bartira Rossi-Bergmann
Affiliations
Ariane de J. Sousa-Batista
Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro—UFRJ, Avenida Carlos Chagas Filho 373, Rio de Janeiro 21941-902, RJ, Brazil
Natalia Arruda-Costa
Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro—UFRJ, Avenida Carlos Chagas Filho 373, Rio de Janeiro 21941-902, RJ, Brazil
Wallace Pacienza-Lima
Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro—UFRJ, Avenida Carlos Chagas Filho 373, Rio de Janeiro 21941-902, RJ, Brazil
Felipe Carvalho-Gondim
Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro—UFRJ, Avenida Carlos Chagas Filho 373, Rio de Janeiro 21941-902, RJ, Brazil
Rosiane F. Santos
Department of Microbiology, Immunology and Parasitology, Universidade do Estado do Rio de Janeiro—UERJ, Avenida Professor Manoel de Abreu 444, Rio de Janeiro 20550-170, RJ, Brazil
Silvia A. G. Da-Silva
Department of Microbiology, Immunology and Parasitology, Universidade do Estado do Rio de Janeiro—UERJ, Avenida Professor Manoel de Abreu 444, Rio de Janeiro 20550-170, RJ, Brazil
Maria Inês Ré
RAPSODEE Center, IMT Mines Albi, CNRS, Jarlard Campus, University of Toulouse, CEDEX 09, F-81013 Albi, France
Bartira Rossi-Bergmann
Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro—UFRJ, Avenida Carlos Chagas Filho 373, Rio de Janeiro 21941-902, RJ, Brazil
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.
