Novel biocompatible anionic polymeric microspheres for the delivery of the HIV-1 Tat protein for vaccine application.
Two novel classes of biocompatible core-shell anionic microspheres, composed of an inner hard insoluble core, either made of poly(styrene) (PS) or poly(methyl methacrylate) (PMMA), and a soft outer tentacular shell made of long soluble negatively charged arms derived from the steric stabilizer, hemisuccinated poly(vinyl alcohol) or Eudragit L100/55, respectively, were prepared by dispersion polymerization and characterized. Five types of these novel microspheres, two made of poly(styrene) and hemisuccinated poly(vinyl alcohol) (A4 and A7), and three made of poly(methyl methacrylate) and Eudragit L100/55 (1D, 1E, H1D), differing for chemical composition, size, and surface charge density were analyzed for the delivery of the HIV-1 Tat protein for vaccine applications. All microspheres reversibly adsorbed the native biologically active HIV-1 Tat protein preventing Tat from oxidation and maintaining its biological activity, therefore increasing the shelf-life of the Tat protein vaccine. The microspheres efficiently delivered Tat intracellularly, and were not toxic in vitro nor in mice, even after multiple administrations. These results indicate that these novel microparticles are safe and represent a promising delivery system for vaccination with Tat, as well as for other subunit vaccines, particularly when a native protein conformation is required.
Caputo
Antonella
A
Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44100, Italy. cpa@unife.it
Brocca-Cofano
Egidio
E
Castaldello
Arianna
A
De Michele
Rita
R
Altavilla
Giuseppe
G
Marchisio
Marco
M
Gavioli
Riccardo
R
Rolen
Ulrika
U
Chiarantini
Laura
L
Cerasi
Aurora
A
Dominici
Sabrina
S
Magnani
Mauro
M
Cafaro
Aurelio
A
Sparnacci
Katia
K
Laus
Michele
M
Tondelli
Luisa
L
Ensoli
Barbara
B
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D001672:Biocompatible Materials; D002470:Cell Survival; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010084:Oxidation-Reduction; D010316:Particle Size; D010587:Phagocytosis; D011487:Protein Conformation; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D001672:Biocompatible Materials; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus