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Tetanus Toxoid Loaded Nanoparticles from Sulfobutylated Poly(Vinyl Alcohol)-Graft-Poly(Lactide-co-Glycolide): Evaluation of Antibody Response After Oral and Nasal Application in Mice
Authors:Jung  Tobias  Kamm  Walter  Breitenbach  Armin  Hungerer  Klaus-Dieter  Hundt   Erika  Kissel   Thomas
Affiliation:(1) Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany;(2) Chiron Behring, Marburg, Germany;(3) Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany;(4) Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, D-35037 Marburg, Germany
Abstract:Purpose. Aim of the study was the evaluation of the potential of novel tetanus toxoid (TT) loaded nanoparticles (NP) for electing an immune response in mice against TT.Methods. Six week-old female Balb/c mice were immunized by oral (p.o.), nasal (i.n.) and intraperitoneal (i.p.) application of TT NP loaded by adsorption. As polymer a novel polyester, sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide), SB(43)-PVAL-g-PLGA was used. Blood samples were collected 4 and 6 weeks after immunization and assayed for serum IgG- as well as IgA antibody titers by ELISA. NP formulations varying in size and loading were compared to alum adsorbates as well as to TT solutions.Results. Both, p.o. and i.n. administration of TT associated NP increased serum titers up to 3 × 103 (IgG) and 2 × 103 (IgA). While small NP induced significantly higher titers then larger ones after oral administration, intermediate NP induced antibodies after nasal application. Of the mucosal routes investigated, i.n. seems to be more promising compared to p.o. immunization.Conclusions. Antigen loaded NP prepared from surface modified polyesters combined with CT show considerable potential as a vaccine delivery system for mucosal immunization. The results warrant further experiments to explore in more detail the potential use of NP as mucosal vaccine delivery system.
Keywords:nanoparticles  biodegradable branched polyester  mucosal immunization  adsorption  tetanus toxoid
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