Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells
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BioMed Central
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Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells Ana Paula F Trombone1,2, Celio L Silva1,2, Luciana P Almeida1,2, Rogerio S Rosada1,2, Karla M Lima1, Constance Oliver3, Maria C Jamur3 and Arlete AM Coelho-Castelo*1,2 Address: 1Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brasil, 2NPT – Núcleo de Pesquisas em Tuberculose – Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brasil and 3Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brasil Email: Ana Paula F Trombone - [email protected]; Celio L Silva - [email protected]; Luciana P Almeida - [email protected]; Rogerio S Rosada - [email protected]; Karla M Lima - [email protected]; Constance Oliver - [email protected]; Maria C Jamur - [email protected]; Arlete AM Coelho-Castelo* - [email protected] * Corresponding author
Published: 20 September 2007 Genetic Vaccines and Therapy 2007, 5:9
doi:10.1186/1479-0556-5-9
Received: 27 June 2007 Accepted: 20 September 2007
This article is available from: http://www.gvt-journal.com/content/5/1/9 © 2007 Trombone et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract This study aimed to demonstrate that microspheres, used as delivery vehicle of DNA-Hsp65/TDM [plasmid DNA encoding heat shock protein 65 (Hsp65) coencapsulated with trehalose dimycolate (TDM) into PLGA microspheres], are widely spread among several organs after intramuscular administration in BALB/c mice. In general, we showed that these particles were phagocytosed by antigen presenting cells, such as macrophages and dendritic cells. Besides, it was demonstrated herein that draining lymph node cells presented a significant increase in the number of cells expressing costimulatory molecules (CD80 and CD86) and MHC class II, and also that the administration of the DNA-Hsp65/TDM and vector/TDM formulations resulted in the upregulation of CD80, CD86 and MHC class II expression when compared to control formulations (vector/TDM and empty). Regarding the intracellular trafficking we observed that following phagocytosis, the microspheres were not found in the late endosomes and/or lysosomes, until 15 days after internalization, and we suggest that these constructions were hydrolysed in early compartments. Overall, these data expand our knowledge on PLGA [poly (lactic-co- glycolic acid)] microspheres as gene carriers in vaccination strateg
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