The effect of poly(D,L-lactide-co-glycolide) microparticles with polyelectrolyte self-assembled multilayer surfaces on the cross-presentation of exogenous antigens.
A surface-engineered particulate delivery system for exogenous antigens was developed in this study. Poly(d,l-lactide-co-glycolide) (PLGA) microparticles containing ovalbumin (OVA) or fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were fabricated by the double emulsion and solvent evaporation method. Encapsulation of the PLGA microparticles was performed by physisorption of multilayers of oppositely charged polyelectrolytes, including polyethylenimine (PEI) and dextran sulfate. Surface charges of the particles after layer-by-layer (LbL) adsorption were determined by the zeta potential measurements. The uptake of these particles by the J774A.1 murine macrophages was examined by fluorescence microscopy. Generation of reactive oxygen species (ROS) in J774A.1 cells was determined by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and hydroethidine (HE). Antigen presentation assays were performed in B3Z cells, a hybridoma of OVA-specific CD8(+) T cells. Results obtained in this study demonstrated an effective ingestion of the PLGA microparticles and enhanced production of ROS in J774A.1 murine macrophages. Treatment of murine bone marrow-derived dendritic cells (BMDCs) with polyelectrolyte-encapsulated PLGA microparticles resulted in an in vitro activation of B3Z cells, demonstrating the feasibility of induction of adaptive immunity for class I major histocompatibility complex (MHC) by surface engineering of microparticulate vaccine delivery.
Yang
Ya-Wun
YW
School of Pharmacy, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei, Taiwan. ywyang@ntu.edu.tw
Hsu
Paul Yueh-Jen
PY
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D016264:Dextran Sulfate / Q000494:pharmacology; D006825:Hybridomas; D019344:Lactic Acid / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000187:drug effects; D051379:Mice; D008863:Microspheres; D010047:Ovalbumin / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011094:Polyethyleneimine / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism; D055672:Static Electricity
D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D010047:Ovalbumin; D016264:Dextran Sulfate