Tissue Distribution of DNA-Hsp65/TDM-loaded PLGA Microspheres and Uptake by Phagocytic Cells

Overview

Journal Genet Vaccines Ther

Publisher Biomed Central

Date 2007 Sep 21

PMID 17880727

Citations 4

Authors

Ana Paula F Trombone

Celio L Silva

Luciana P Almeida

Rogerio S Rosada

Karla M Lima

Constance Oliver

Maria C Jamur

Arlete A M Coelho-Castelo

Affiliations

Soon will be listed here.

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 up-regulation 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 strategies, as well as open perspectives for their potential use in clinical practice.

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