TY - JOUR
T1 - Novel biocompatible anionic polymeric microspheres for the delivery of the HIV-1 Tat protein for vaccine application
AU - Caputo, Antonella
AU - Brocca-Cofano, Egidio
AU - Castaldello, Arianna
AU - De Michele, Rita
AU - Altavilla, Giuseppe
AU - Marchisio, Marco
AU - Gavioli, Riccardo
AU - Rolen, Ulrika
AU - Chiarantini, Laura
AU - Cerasi, Aurora
AU - Dominici, Sabrina
AU - Magnani, Mauro
AU - Cafaro, Aurelio
AU - Sparnacci, Katia
AU - Laus, Michele
AU - Tondelli, Luisa
AU - Ensoli, Barbara
N1 - Funding Information:
This work was supported by grants from the Istituto Superiore di Sanità, from The Italian Concerted Action on HIV-AIDS Vaccine Development (ICAV), from the Associazione Nazionale per la Lotta contro l’AIDS (ANLAIDS), CIB 2002 project and from MURST 60%. We are grateful to E. Fanales, S. Moretti, V. Fiorelli, F. Nappi (Istituto Superiore di Sanità, Roma) for all Tat testing, to C. Celeghini and S. Capitani (University of Ferrara) for assistance at the fluorescent and confocal microscopes, and to L. Magnani (CNR ISOF), R. Voltan, M. Fabris and P.C. Marconi (University of Ferrara) for helpful discussion.
PY - 2004/7/29
Y1 - 2004/7/29
N2 - 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.
AB - 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.
KW - Biocompatible microspheres
KW - HIV-1 Tat protein
KW - Vaccine
UR - https://www.scopus.com/pages/publications/3142538773
U2 - 10.1016/j.vaccine.2003.12.025
DO - 10.1016/j.vaccine.2003.12.025
M3 - Article
SN - 0264-410X
VL - 22
SP - 2910
EP - 2924
JO - Vaccine
JF - Vaccine
IS - 21-22
ER -
