title: Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis.
abstract: Surface modifications of poly(lactide-co-glycolide) microparticles with different polycationic electrolytes have mainly been studied for conjugation to antigens and/or adjuvants. However, the in vivo immunological effects of using surface charged particles have not been address yet. In this study, microparticles were coated or not with protamine, a cationic and arginine-rich electrolyte that confers microparticles with a positively surface charge. We then evaluated the potential of protamine-coatings to assist the induction of immune responses in mice. Interestingly, enhanced antibodies and T-cell responses were observed in mice treated with the coated particles. In vitro studies suggested that the improved immunological performance was mediated by an increased uptake. Indeed, protamine-coated particles that carried a plasmid were even internalised into non-phagocytic cells and to cause their transfection. These results open the way for further research into a novel technology that combines the use protamine for facilitated cell penetration of that and biodegradable microparticles for prolonged antigen or drug release.
authors.affiliation: Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Martínez Gómez
authors.forename: Noémi
authors.initials: N
authors.lastname: Csaba
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Anke
authors.initials: A
authors.lastname: Sichelstiel
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004247:DNA / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology; D000071228:Polyelectrolytes; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011479:Protamines / Q000737:chemistry / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013499:Surface Properties; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014162:Transfection
chemical_list: D000941:Antigens; D004247:DNA; D004337:Drug Carriers; D049452:Green Fluorescent Proteins; D019344:Lactic Acid; D011073:Polyamines; D000071228:Polyelectrolytes; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011479:Protamines; D011948:Receptors, Antigen, T-Cell