Crucial CD8(+) T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis

Autor: Daniela Barros, Ricardo Jorge Dinis-Oliveira, Maria Teresa Baltazar, Anabela Cordeiro-da-Silva, Sofia A. Costa Lima, Joana Cunha, Ricardo Silvestre
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Rok vydání: 2013
Předmět:
CD8-Positive T-Lymphocytes/metabolism
Materials science
Biomedical Engineering
Amphotericin B/therapeutic use
Antiprotozoal Agents
Pharmaceutical Science
Medicine (miscellaneous)
Amphotericin B/chemistry
Bioengineering
macromolecular substances
Pharmacology
T-Lymphocytes
Cytotoxic/metabolism
CD8-Positive T-Lymphocytes
03 medical and health sciences
chemistry.chemical_compound
Mice
Cd8 t lymphocyte
In vivo
Amphotericin B
Antiprotozoal Agents/therapeutic use
medicine
Cytotoxic T cell
Animals
General Materials Science
Antiprotozoal Agents/chemistry
030304 developmental biology
0303 health sciences
Mice
Inbred BALB C
030306 microbiology
technology
industry
and agriculture
Nanospheres/chemistry
medicine.disease
Leishmaniasis
Visceral/drug therapy
In vitro
Leishmaniasis
Visceral/immunology
PLGA
Visceral leishmaniasis
chemistry
Immunology
Molecular Medicine
Leishmaniasis
Visceral
CD8
Nanospheres
medicine.drug
T-Lymphocytes
Cytotoxic
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 1549-9642
Popis: This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was > 90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8 + - but not CD4 + -T lymphocytes. Overall, we demonstrate a crucial role for CD8 + cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. This work was supported by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the Operational Competitiveness Program-COMPETE and by national funds through Fundação para a Ciência e a Tecnologia under projects FCOMP-01-0124-FEDER-015718 (PTDC/SAU- ENB/113151/2009) and Fundação Caloust Gulbenkian under project P-105348/2009. D.B. was supported by FCOMP-01-0124-FEDER-015718 (PTDC/SAU-ENB/113151/2009) project. S.A.C.L, J.C. T.B. and R.D-O. were supported by SFRH/BPD/37880/2007, SFRH/BD/48626/2008, SFRH/BD/65387/2009 and IF/01147/2013, respectively. R.S. was supported by Programa Ciência, financed by Programa Operacional Potencial Humano–Quadro de Referência Estratégica Nacional-Tipologia 4.2-Promoção do Emprego Científico, co-funded by Fundo Social Europeu and national funding from the Ministry of Science, Technology and Higher Education.
Databáze: OpenAIRE
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