Surface functionalization of polymeric nanospheres modulates macrophage activation: Relevance in Leishmaniasis therapy
Autor: | Sofia A. Costa Lima, Anabela Cordeiro-da-Silva, Daniela Barros |
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Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Drug Carriers/chemistry
Male Leishmaniasis/drug therapy Polymers Medicine (miscellaneous) Mannans/chemistry 02 engineering and technology Macrophages/immunology Mannans chemistry.chemical_compound Mice Macrophages/drug effects Polylactic Acid-Polyglycolic Acid Copolymer Polymers/chemistry Fluorescence microscope Macrophage General Materials Science Leishmaniasis Cells Cultured Mannan 0303 health sciences Drug Carriers Mice Inbred BALB C Macrophage Activation/drug effects Mannans/immunology Mannose/immunology 021001 nanoscience & nanotechnology 3. Good health PLGA Cytokines 0210 nano-technology Polyglycolic Acid/chemistry Nanospheres Mannose/chemistry Materials science Lactic Acid/chemistry Biomedical Engineering Antiprotozoal Agents Bioengineering Development Amphotericin B/administration & dosage Endocytosis 03 medical and health sciences Cytokines/immunology Amphotericin B Animals Antiprotozoal Agents/chemistry Lactic Acid 030304 developmental biology Carbodiimide Leishmaniasis/immunology Macrophages Nanospheres/chemistry Mannosamine Macrophage Activation Molecular biology chemistry Lactic Acid/immunology Nanocarriers Mannose Polyglycolic Acid |
Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
Popis: | To characterize the production and application of carbohydrate functionalized poly(d,l-lactide-co-glycolide) (PLGA) nanospheres as immune-modulatory mediators in the treatment of visceral leishmaniasis (VL). Materials & methods: PLGA nanospheres were prepared by nanoprecipitation and surface functionalized with mannose, mannan or mannosamine moieties using a carbodiimide reaction. Flow cytometry and fluorescence microscopy revealed the interaction of these nanospheres with macrophages. Results: The nanocarriers were taken up by murine primary macrophages using clathrin-mediated endocytosis. Co-culture of macrophages with carbohydrate-functionalized nanospheres led to their activation and production of pro-inflammatory cytokines. One dose of amphotericin B-loaded on mannan-functionalized nanospheres resulted in an efficacy VL therapy. Conclusion: This approach provides a promising therapy for VL and a new therapeutic nanoplatform for obligate intracellular pathogens. 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). D Barros was supported by FCOMP-01- 0124-FEDER-015718 (PTDC/SAU-ENB/113151/2009) project. SA Costa Lima was supported by SFRH/BPD/37880/2007 and by QREN under contract NORTE-07-0124-FEDER-000067. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. |
Databáze: | OpenAIRE |
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