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

• Published in: Journal of drug delivery science and technology Vol. 86; p. 104704
• Main Authors: Sessevmez, Melike, Sinani, Genada, Okyar, Alper, Alpar, H. Oya, Cevher, Erdal
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-09-2023
• Subjects: Chitosan; Curdlan; Immune response; Nanoparticle; Nasal; Vaccine; Vaccine; Nasal; Immune response; Chitosan; Curdlan; Nanoparticle
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2023.104704

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.
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