title: Uptake of poly(D,L-lactic-co-glycolic acid) microspheres by antigen-presenting cells in vivo.
abstract: Dendritic cells are the most potent antigen-presenting cells (APC) and the most effective stimulators of primary T cell responses. Based on the strong influence of the APC on the immune response, we investigated cellular uptake of a biodegradable antigen delivery system, poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, at two sites of injection: intraperitoneal and intradermal. We hypothesized that a fluorescent probe, tetramethylrhodamine labeled dextran, loaded in PLGA microspheres would be taken up by APCs and thereby provide a means for studying cellular uptake of PLGA microspheres in vivo. Phagocytic load and cell phenotype were determined using flow cytometry and confocal laser scanning microscopy. The results revealed cellular uptake of tetramethylrhodamine dextran loaded PLGA microspheres at both injection sites. After intraperitoneal immunization, the predominant cell phagocytosing PLGA microspheres in the peritoneal cavity was the macrophage whereas the intradermal immunization resulted in uptake of PLGA microspheres by dendritic cells. Hence, these results suggest that the profile for cellular uptake varies with the site of injection. More importantly, this study provides direct and conclusive evidence of uptake of PLGA microspheres by the most potent APC, the dendritic cell.
authors.affiliation: 3118 Dentistry/Pharmacy Centre, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Newman
authors.forename: Praveen
authors.initials: P
authors.lastname: Elamanchili
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
authors.forename: John
authors.initials: J
authors.lastname: Samuel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000378:metabolism*
chemical_list: D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid