Induction of humoral and cell-mediated immunity in mice by chitosan-curdlan composite nanoparticles administered intranasally and subcutaneously


SESSEVMEZ M., Sinani G., OKYAR A., Alpar H. O., CEVHER E.

Journal of Drug Delivery Science and Technology, cilt.86, 2023 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 86
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.jddst.2023.104704
  • Dergi Adı: Journal of Drug Delivery Science and Technology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Anahtar Kelimeler: Chitosan, Curdlan, Immune response, Nanoparticle, Nasal, Vaccine
  • İstanbul Üniversitesi Adresli: Evet

Özet

Infectious diseases seriously threaten human life. The need for novel delivery systems and adjuvants suitable to be used in clinic for antigens remains a challenge. Among various attempts that have been made to provide optimum immune responses for protein antigens with poor immunogenicity, polymeric nanoparticles offer great opportunities. In this study, carboxymethyl curdlan (CMC) as a polyanionic polymer and chitosan chloride (CC) and N-trimethyl chitosan (TMC) as polycationic polymers were synthesised in-house and composite nanoparticles (CC-CMC-BSA and TMC-CMC-BSA) loaded with bovine serum albumin (BSA) as a model antigen were prepared via polyelectrolyte complexation and reported here for the first time. Nanoparticles with an average size ranging from 153 nm to 615 nm, positive surface charge (from +24 mV to +55 mV) and encapsulation efficiency as high as 90% were obtained depending on the concentration of polymers in the formulation. The nanoparticles showed good physical stability for three months and low toxicity in Calu-3 and A549 cells. Furthermore, SDS integrity of antigen was maintained. In vivo studies in mice indicated that nasal and subcutaneous administration of composite nanoparticles could provide long-term humoral and cellular immunity as determined by serum antibody titres (IgG, IgG1, IgG2a) and cytokine (IL-2, IL-4, IL-6, IL-10 and IFN-γ) levels. Elevated sIgA levels after nasal administration of the nanoparticles showed that mucosal immunity was successfully stimulated. These findings suggest that chitosan-curdlan composite nanoparticles show optimum properties to be used as nanovaccine for nasal immunisation of protein antigens.