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Biodegradable microspheres containing leukotriene B(4) and cell-free antigens from Histoplasma capsulatum activate murine bone marrow-derived macrophages.
MedLine Citation:
PMID:  22009111     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Because of the potential protective role of leukotrienes (LTs) in histoplasmosis and the therapeutic and prophylactic effects of cell-free antigens from Histoplasmacapsulatum (CFAgs), the aim of this study was to develop and characterise biodegradable LTB(4)/CFAgs-loaded microspheres (MS) that could promote cellular activation for future immunisation purposes. LTB(4)/CFAgs-loaded MS that were developed through a double emulsion/extraction process were characterised according to their size, zeta potential, morphology, entrapment efficiency and in vitro release kinetics. We evaluated the uptake of LTB(4)/CFAgs-loaded MS by bone marrow derived-macrophages (BMDMϕ). The TNF-α and chemokines, and nitrite production, in the supernatant of BMDMϕ cultures were analysed by enzyme-linked immunosorbent assay (ELISA) and Griess reaction, respectively. We found an instantaneous release of CFAgs and a prolonged release of LTB(4) from the poly-(d,l-lactide-co-glycolide) (PLGA) MS. The microencapsulation process did not alter the zeta potential nor the spherical morphology of the MS. The appropriate size of the LTB(4)/CFAgs-loaded MS (smaller than 10μm) enabled the efficient uptake by BMDMϕ and also induced TNF-α, CXCL1/KC, CCL2/MCP-1, CCL5/RANTES and nitrite oxide release by these cells. In conclusion, the biodegradable LTB(4)/CFAgs-loaded MS were able to efficiently activate murine BMDMϕ and thereby have the potential to be used in an effective vaccine against H. capsulatum infection.
Authors:
Daiane F Dos Santos; Claudia da S Bitencourt; Guilherme M Gelfuso; Priscilla A T Pereira; Patrícia R M de Souza; Carlos A Sorgi; Roberto Nicolete; Lúcia H Faccioli
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-8
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  -     ISSN:  1879-0720     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Affiliation:
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
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