title: Immunoadjuvant activity of the nanoparticles' surface modified with mannan.
abstract: Mannan (MN) is the natural ligand for mannose receptors, which are widely expressed on dendritic cells (DCs). The purpose of this study was to assess the effect of formulation parameters on the immunogenicity of MN-decorated poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to stimulate DC phenotypic as well as functional maturation. For this purpose, NPs were formulated from either ester-terminated or COOH-terminated PLGA. Incorporation of MN in NPs was achieved through encapsulation, physical adsorption or chemical conjugation. Murine bone marrow derived DCs (BMDCs) were treated with various NP formulations and assessed for their ability to up-regulate DC cell surface markers, secrete immunostimulatory cytokines and to activate allogenic T cell responses. DCs treated with COOH-terminated PLGA-NPs containing chemically conjugated MN (MN-Cov-COOH) have shown superior performance in improving DC biological functions, compared to the rest of the formulations tested. This may be attributed to the higher level of MN incorporation in the former formulation. Incorporation of MN in PLGA NPs through chemical conjugation can lead to enhanced DC maturation and stimulatory function. This strategy may be used to develop more effective PLGA-based vaccine formulations.
authors.affiliation: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Azita
authors.initials: A
authors.lastname: Haddadi
authors.forename: Samar
authors.initials: S
authors.lastname: Hamdy
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ghotbi
authors.forename: John
authors.initials: J
authors.lastname: Samuel
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007109:Immunity / Q000187:drug effects* / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D008351:Mannans / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D016207:Cytokines; D008351:Mannans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid