Chitosan-based Nanoparticles in Mucosal Vaccine Delivery

Document Type : Review Article


1 Department of Medical Nanotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

2 Department of Medical Nanotechnology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran


Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Nowadays, the use of vaccines has been widely investigated for the prevention of different infectious diseases, infertility, immune disorders, malignancies, and allergies. Broad-spectrum adjuvant substances have been studied for immune system stimulation with a greater efficiency against specific antigens. Various adjuvants have been developed such as inorganic, oil-based, and emulsion adjuvants, bacterial products and their derivatives, cytokines, cytosine-guanine dinucleotide (CpG) motifs, and particulate systems. Mucosal vaccine delivery is an alternative route to induce both humoral and cellular immune responses. Applying nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery, and consequently, more specific release of the agent of interest. Chitosan nanoparticles have immunological activity and mucoadhesive properties. They have been used as a mucosal vaccine delivery system for many antigens. This review provides an overview of the recent advances in chitosan nanoparticles as a novel mucosal vaccine delivery system.


Main Subjects

Article Title [French]

Nanoparticules à base de Chitosan dans l'Administration de Vaccins Muqueux

Abstract [French]

La plupart des maladies infectieuses sont causées par des infiltrations pathogènes provenant du tractus muqueux. De nos jours, l'utilisation de vaccins a été largement étudiée pour la prévention de différentes maladies infectieuses, de l'infertilité, des troubles immunitaires, des tumeurs malignes et des allergies. Des substances adjuvantes à large spectre ont été étudiées pour la stimulation du système immunitaire avec une efficacité accrue contre des antigènes spécifiques. Divers adjuvants ont été développés, tels que des adjuvants inorganiques, à base d'huile et d'émulsion, des produits bactériens et leurs dérivés, des cytokines, des motifs cytosine-guanine dinucléotide (CpG) et des systèmes particulaires. L'administration du vaccin muqueux est une voie alternative pour induire des réponses immunitaires humorales et cellulaires. L'application de nanoparticules dans les formulations de vaccins permet non seulement d'améliorer la stabilité et l'immunogénicité des antigènes, mais également de cibler la délivrance et, par conséquent, la libération plus spécifique de l'agent d'intérêt. Les nanoparticules de chitosan ont une activité immunologique et des propriétés mucoadhésives. Ils ont été utilisés comme système d'administration de vaccins muqueux pour de nombreux antigènes. Cet examen fournit un aperçu des avancées récentes dans les nanoparticules de chitosane en tant que nouveau système d'administration de vaccins muqueux.

Keywords [French]

  • Adjuvant
  • Nanoparticule de Chitosane
  • Administration de Vaccin Muqueux
Abruzzo, A., Cerchiara, T., Bigucci, F., Gallucci, M.C., Luppi, B., 2015. Mucoadhesive Buccal Tablets Based on Chitosan/Gelatin Microparticles for Delivery of Propranolol Hydrochloride. J Pharm Sci 104, 4365-4372.
Akagi, T., Baba, M., Akashi, M., 2007. [Development of vaccine adjuvants using polymeric nanoparticles and their potential applications for anti-HIV vaccine]. Yakugaku Zasshi 127, 307-317.
Akagi, T., Baba, M., Akashi, M., 2012. Biodegradable nanoparticles as vaccine adjuvants and delivery systems: regulation of immune responses by nanoparticle-based vaccine, Springer.
Amidi, M., Romeijn, S.G., Verhoef, J.C., Junginger, H.E., Bungener, L., Huckriede, A., et al., 2007. N-trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: biological properties and immunogenicity in a mouse model. Vaccine 25, 144-153.
Aucouturier, J., Dupuis, L., Ganne, V., 2001. Adjuvants designed for veterinary and human vaccines. Vaccine 19, 2666-2672.
Bansal, V., Sharma, P.K., Sharma, N., Pal, O.P., Malviya, R., 2011. Applications of chitosan and chitosan derivatives in drug delivery. Adv Biol Res 5, 28-37.
Chikaura, H., Nakashima, Y., Fujiwara, Y., Komohara, Y., Takeya, M., Nakanishi, Y., 2016. Effect of particle size on biological response by human monocyte-derived macrophages. Biosurface and Biotribology 2, 18-25.
Deng, Q.-y., Zhou, C.-r., Luo, B.-h., 2006. Preparation and Characterization of Chitosan Nanoparticles Containing Lysozyme. Pharmaceutical Biology 44, 336-342.
Des Rieux, A., Fievez, V., Garinot, M., Schneider, Y.J., Preat, V., 2006. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release 116, 1-27.
Dyer, A.M., Hinchcliffe, M., Watts, P., Castile, J., Jabbal-Gill, I., Nankervis, R., et al., 2002. Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 19, 998-1008.
Fernandez-Urrusuno, R., Calvo, P., Remunan-Lopez, C., Vila-Jato, J.L., Alonso, M.J., 1999. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm Res 16, 1576-1581.
Islam, M.A., Firdous, J., Choi, Y.J., Yun, C.H., Cho, C.S., 2012. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review. Int J Nanomedicine 7, 6077-6093.
Kammona, O., Kiparissides, C., 2012. Recent advances in nanocarrier-based mucosal delivery of biomolecules. J Control Release 161, 781-794.
Makhlof, A., Tozuka, Y., Takeuchi, H., 2011. Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur J Pharm Sci 42, 445-451.
Mohammadpourdounighi, N., Behfar, A., Ezabadi, A., Zolfagharian, H., Heydari, M., 2010. Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom. Nanomedicine 6, 137-143.
Nandedkar, T.D., 2009. Nanovaccines: recent developments in vaccination. J Biosci 34, 995-1003.
Neutra, M.R., Kozlowski, P.A., 2006. Mucosal vaccines: the promise and the challenge. Nat Rev Immunol 6, 148-158.
Parez, N., Fourgeux, C., Mohamed, A., Dubuquoy, C., Pillot, M., Dehee, A., et al., 2006. Rectal immunization with rotavirus virus-like particles induces systemic and mucosal humoral immune responses and protects mice against rotavirus infection. J Virol 80, 1752-1761.
Perrie, Y., Mohammed, A.R., Kirby, D.J., McNeil, S.E., Bramwell, V.W., 2008. Vaccine adjuvant systems: enhancing the efficacy of sub-unit protein antigens. Int J Pharm 364, 272-280.
Rahimian, S., Fransen, M.F., Kleinovink, J.W., Christensen, J.R., Amidi, M., Hennink, W.E., et al., 2015. Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation. J Control Release 203, 16-22.
Sandri, G., Bonferoni, M.C., Ferrari, F., Rossi, S., Mori, M., Caramella, C., 2015. Opportunities offered by chitosan-based nanotechnology in mucosal/skin drug delivery. Curr Top Med Chem 15, 401-412.
Shim, B.S., Choi, Y., Cheon, I.S., Song, M.K., 2013. Sublingual delivery of vaccines for the induction of mucosal immunity. Immune Netw 13, 81-85.
Sonaje, K., Chen, Y.J., Chen, H.L., Wey, S.P., Juang, J.H., Nguyen, H.N., et al., 2010. Enteric-coated capsules filled with freeze-dried chitosan/poly(gamma-glutamic acid) nanoparticles for oral insulin delivery. Biomaterials 31, 3384-3394.
Tonnis, W.F., Kersten, G.F., Frijlink, H.W., Hinrichs, W.L., de Boer, A.H., Amorij, J.P., 2012. Pulmonary vaccine delivery: a realistic approach? J Aerosol Med Pulm Drug Deliv 25, 249-260.
Vila, A., Sanchez, A., Janes, K., Behrens, I., Kissel, T., Vila, Jato, J.L., et al., 2004. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm 57, 123-131.
Wong, T.W., 2009. Chitosan and its use in design of insulin delivery system. Recent Pat Drug Deliv Formul 3, 8-25.
Zhang, L., Zeng, Z., Hu, C., Bellis, S.L., Yang, W., Su, Y., et al., 2016. Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines. Biomaterials 77, 307-319.
Zhang, X., Zhang, H., Wu, Z., Wang, Z., Niu, H., Li, C., 2008. Nasal absorption enhancement of insulin using PEG-grafted chitosan nanoparticles. Eur J Pharm Biopharm 68, 526-534.