TMC–MCC (N-trimethyl chitosan–mono-N-carboxymethyl chitosan) nanocomplexes for mucosal delivery of vaccines |
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Authors: | Burcu Say n, Satyanarayana Somavarapu, Xiong Wei Li, Dorothea Sesardic, Sevda enel,Oya H. Alpar |
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Affiliation: | aHacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, 06100, Turkey;bSchool of Pharmacy, University of London, 29-39, Brunswick Square, London, WC1N 1AX, UK;cDivision of Bacteriology, NIBSC, Blance Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK |
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Abstract: | In this study, for the first time, TMC/MCC complex nanoparticles as a delivery system and as an adjuvant were developed and evaluated to obtain systemic and mucosal immune responses against nasally administered tetanus toxoid (TT). Nanoparticles were developed by complexation between the oppositely charged chitosan derivatives, N-trimethyl chitosan (TMC, polycationic) and mono-N-carboxymethyl chitosan (MCC, polyampholytic) without using any crosslinker for mucosal vaccination. The cellular viability was found to be higher with TMC/MCC complex compared to that of MCC and TMC alone. Size, zeta potential and morphology of the nanoparticles were investigated as a function of preparation method. Nanoparticles with high loading efficacy (95%) and positively charged surface were obtained with an average particle size of 283 ± 2.5 nm. The structural integrity of the TT in the nanoparticles was confirmed by SDS–PAGE electrophoresis analysis. Cellular uptake studies indicated that FITC-BSA loaded nanoparticles were effectively taken up into the mouse Balb/c monocyte macrophages. Mice were nasally immunized with TT loaded TMC/MCC complex nanoparticles and compared to that of TMC and MCC nanoparticles. TMC/MCC complex nanoparticles were shown to induce both the mucosal and systemic immune response indicating that this newly developed system has potential for mucosal administration of vaccines. |
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Keywords: | Mucosal immunization Nanoparticles Chitosan Chitosan derivatives Tetanus toxoid N-trimethyl chitosan Mono-N-carboxymethyl chitosan Nasal vaccination Nanocomplex |
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