Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies

Cevher E., Salomon S. K., Somavarapu S., Brocchini S., Alpar H. O.

JOURNAL OF MICROENCAPSULATION, cilt.32, sa.8, ss.769-783, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 32 Sayı: 8
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/02652048.2015.1073393
  • Dergi Adı: JOURNAL OF MICROENCAPSULATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.769-783
  • Anahtar Kelimeler: Carboxymethyl pullulan, chitosan derivatives, intramuscular immunisation, nanoparticles, nasal immunisation, polyion complexation, NASOPHARYNGEAL LYMPHOID-TISSUE, IMMUNE-RESPONSES, MUCOSAL VACCINE, CPG OLIGODEOXYNUCLEOTIDES, POLYELECTROLYTE COMPLEXES, MOLECULAR-WEIGHT, HEPATITIS-B, INTRANASAL VACCINATION, ABSORPTION ENHANCER, TMC NANOPARTICLES
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 Th-1/Th-2 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.