Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.
Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Istanbul University , Istanbul , Turkey .
Erdal
E
Cevher
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , United Kingdom .|c GlaxoSmithKline , London , United Kingdom , and.
Stefan K
SK
Salomon
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , United Kingdom .
Satyanarayana
S
Somavarapu
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , United Kingdom .
Steve
S
Brocchini
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , United Kingdom .|d Department of Pharmaceutics, Faculty of Pharmacy , Kemerburgaz University , Istanbul , Turkey.
H Oya
HO
Alpar
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D004168:Diphtheria Toxoid / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D053761:Nanocomposites / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; C408982:CPG-oligonucleotide; D004168:Diphtheria Toxoid; D009838:Oligodeoxyribonucleotides; D048271:Chitosan
Carboxymethyl pullulan; chitosan derivatives; intramuscular immunisation; nanoparticles; nasal immunisation; polyion complexation