title: Microneedle-mediated transcutaneous immunization with plasmid DNA coated on cationic PLGA nanoparticles.
abstract: Previously, it was shown that microneedle-mediated transcutaneous immunization with plasmid DNA can potentially induce a stronger immune response than intramuscular injection of the same plasmid DNA. In the present study, we showed that the immune responses induced by transcutaneous immunization by applying plasmid DNA onto a skin area pretreated with solid microneedles were significantly enhanced by coating the plasmid DNA on the surface of cationic nanoparticles. In addition, the net surface charge of the DNA-coated nanoparticles significantly affected their in vitro skin permeation and their ability to induce immune responses in vivo. Transcutaneous immunization with plasmid DNA-coated net positively charged nanoparticles elicited a stronger immune response than with plasmid DNA-coated net negatively charged nanoparticles or by intramuscular immunization with plasmid DNA alone. Transcutaneous immunization with plasmid DNA-coated net positively charged nanoparticles induced comparable immune responses as intramuscular injection of them, but transcutaneous immunization was able to induce specific mucosal immunity and a more balanced T helper type 1 and type 2 response. The ability of the net positively charged DNA-coated nanoparticles to induce a strong immune response through microneedle-mediated transcutaneous immunization may be attributed to their ability to increase the expression of the antigen gene encoded by the plasmid and to more effectively stimulate the maturation of antigen-presenting cells.
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX 78712, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Piyanuch
authors.initials: P
authors.lastname: Wonganan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandoval
authors.forename: Xinran
authors.initials: X
authors.lastname: Li
authors.forename: Saijie
authors.initials: S
authors.lastname: Zhu
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004247:DNA / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009339:Needles; D010957:Plasmids; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D000644:Quaternary Ammonium Compounds; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D001616:beta-Galactosidase; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane