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S. Dehghan,M. Tavassoti Kheiri,M. Tabatabaiean,S. Darzi,M. Tafaghodi 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.8
The objective of this study was to develop andstatistically optimize chitosan nanospheres. For this purposechitosan powder was turned into nanospheres using tripolyphosphateas a crosslinker and through ionic gelation. D-optimal response surface design was applied to optimizethe nanospheres. Their size and polydispersity index (PDI)were measured as the dependant variables. Then the inactivatedinfluenza virus and/or CpG ODN or Quillaja saponin(QS) were incorporated into the chitosan nanospheres. Therelease profiles of the antigen and both adjuvants wereobtained. The toxicity of the formulations was tested byXTT using Calu 6 cell lines. The size distribution and PDIof plain chitosan nanospheres was 581.1 ± 32.6 and0.478 ± 0.04. After 4 h the release of antigen, QS and CpGfrom the chitosan matrix were 33, 36 and 62 %, respectively. The inactivated virus remained intact during preparation,as revealed by the SDS-PAGE method. Differentialscanning calorimetry and Fourier Transform InfraredSpectroscopy indicated no serious structural changes in thechitosan carrier in the presence of either the antigen or theimmunoadjuvants. Although the antigen loaded into chitosannanospheres showed slight cytotoxicity on lung-cancercells, co-encapsulation of the adjuvant (especially CpG)lowered this effect. The results demonstrated that chitosanas a carrier and immunostimulator, along with CpG or QSadjuvants, creates a potential influenza vaccine deliverysystem which can be administered nasally.