title: Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system.
abstract: The study reported here aimed to develop an optimized nanoparticle delivery system for amphotericin B (AmpB) using a polyelectrolyte complexation technique. For this, two oppositely charged polymers presenting anti-leishmanial activity - chitosan (Cs) and chondroitin sulfate (ChS) - were used: Cs as a positively charged polymer and ChS as a negatively charged polymer. The chitosan (NQ) nanoparticles, chitosan-chondroitin sulfate (NQC) nanoparticles, and chitosan-chondroitin sulfate-amphotericin B (NQC-AmpB) nanoparticles presented a mean particle size of 79, 104, and 136 nm, respectively; and a polydispersity index of 0.2. The measured zeta potential of the nanoparticles indicated a positive charge in their surface, while scanning and transmission electron microscopy revealed spherical nanoparticles with a smooth surface. Attenuated total reflectance-Fourier transform infrared spectroscopy analysis showed an electrostatic interaction between the polymers, whereas the release profile of AmpB from the NQC-AmpB nanoparticles showed a controlled release. In addition, the Cs; ChS; and NQ, NQC, and NQC-AmpB nanoparticles proved to be effective against promastigotes of Leishmania amazonensis and Leishmania chagasi, with a synergistic effect observed between Cs and ChS. Moreover, the applied NQ, NQC, and NQC-AmpB compounds demonstrated low toxicity in murine macrophages, as well as null hemolytic activity in type O(+) human red blood cells. Pure AmpB demonstrated high toxicity in the macrophages. The results show that cells infected with L. amazonensis and later treated with Cs, ChS, NQ, NQC, NQC-AmpB nanoparticles, or pure AmpB presented with a significant reduction in parasite number in the order of 24%, 31%, 55%, 66%, 90%, and 89%, respectively. The data presented indicate that the engineered NQC-AmpB nanoparticles could potentially be used as an alternative therapy to treat leishmaniasis, mainly due its low toxicity to mammals' cells.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Ribeiro
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Chávez-Fumagalli
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Diogo G
authors.initials: DG
authors.lastname: Valadares
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juçara R
authors.initials: JR
authors.lastname: França
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lívia B
authors.initials: LB
authors.lastname: Rodrigues
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Duarte
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Lage
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Pedro H R
authors.initials: PH
authors.lastname: Andrade
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Lage
authors.affiliation: Programa de Pós-Graduação em Patologia Humana, Universidade Federal da Bahia, Salvador, Bahia, Brazil ; Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Leonardo V
authors.initials: LV
authors.lastname: Arruda
authors.affiliation: Programa de Pós-Graduação em Patologia Humana, Universidade Federal da Bahia, Salvador, Bahia, Brazil ; Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Abánades
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lourena E
authors.initials: LE
authors.lastname: Costa
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Vivian T
authors.initials: VT
authors.lastname: Martins
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carlos A P
authors.initials: CA
authors.lastname: Tavares
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil ; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rachel O
authors.initials: RO
authors.lastname: Castilho
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil ; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil ; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: André A G
authors.initials: AA
authors.lastname: Faraco
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects; D007894:Leishmania mexicana / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D014344:Trypanocidal Agents / Q000008:administration & dosage*
chemical_list: D014344:Trypanocidal Agents; D000666:Amphotericin B; D002809:Chondroitin Sulfates; D048271:Chitosan
keywords: Leishmania spp; amphotericin B; chitosan; chondroitin; nanoparticles