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

Pharm Res. 2001 Mar;18(3):352-60. doi: 10.1023/a:1011063232257.

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 x 10(3) (IgG) and 2 x 10(3) (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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Intranasal
  • Administration, Oral
  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Chemical Phenomena
  • Chemistry, Physical
  • Drug Delivery Systems
  • Enzyme-Linked Immunosorbent Assay
  • Excipients
  • Female
  • Immunity, Mucosal
  • Immunization
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Microspheres
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Polyvinyl Alcohol / chemistry*
  • Tetanus / immunology
  • Tetanus Toxoid / administration & dosage*
  • Tetanus Toxoid / immunology

Substances

  • Antibodies, Bacterial
  • Excipients
  • Polymers
  • Tetanus Toxoid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyvinyl Alcohol