Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

International Journal of Nanomedicine Dovepress open access to scientific and medical research R e v iew International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review This article was published in the following Dove Press journal: International Journal of Nanomedicine 12 December 2012 Number of times this article has been viewed Mohammad Ariful Islam 1–3,* Jannatul Firdous 1–3,* Yun-Jaie Choi 1 Cheol-Heui Yun 1–4 Chong-Su Cho 1,2 Department of Agricultural Biotechnology, 2Research Institute for Agriculture and Life Sciences, 3Center for Food and Bioconvergence, 4World Class University Biomodulation Program, Seoul National University, Seoul, South Korea 1 *These authors contributed equally to this work Introduction Correspondence: Cheol-Heui Yun; Chong-Su Cho Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, South Korea Tel +82 2 880 4802 (CHY); +82 2 880 4868 (CSC) Fax +82 2 875 2494 (CSC) Email (CHY); (CSC) submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/IJN.S38330 Powered by TCPDF (www.tcpdf.org) Abstract: Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. Keywords: chitosan microspheres, oral, nasal, vaccine delivery, mucosal and systemic immune responses Vaccination is cost-effective, and probably the best preventable strategy against most diseases.1 Traditionally, vaccines are administered parenterally via an intramuscular or subcutaneous route.2,3 This process of vaccine delivery incurs difficulties such as needle phobia, low patient compliance, short half-life, potential contamination while using needles, and a necessity for highly trained personnel. As a result, oral and nasal vaccination has been paid considerable attention as a way to overcome such potential drawbacks and eliminate the problems associated with parenteral administration of vaccines.4 Better yet, parenteral vaccination mostly stimulates systemic immunity, whereas mucosal vaccination tends to confer both systemic and mucosal immune responses.5 In regard to mucosal administration of protein drugs or vaccines, microspheres are well known for their controlled delivery formulation,6–8 which would provide a longlasting boosting effect and enhance the effectiveness of the immune response against infectious diseases.8 Chitosan has well-defined properties including bioavailability, biocompatibility, low cost, and an ability to open the intracellular tight junction; therefore, it has been suggested as a suitable polymeric material for mucosal delivery.9 Desirable properties International Journal of Nanomedicine 2012:7 6077–6093 6077 © 2012 Islam et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Islam et al of chitosan can be determined from its molecular weight (MW) and degree of deacetylation (DD). It has been reported that high MW chitosan enhances the absorption of various compounds across the mucosal barrier.9,10 Due to its cationic property, positively charged chitosan would have an electrostatic interaction with the negatively charged mucosal surface.11 Moreover, chitosan possesses mucoadhesivity, beneficial for prolonging the retention time at the mucosal area for a controlled and sustained therapeutic effect.4 Nontoxicity is another prerequisite property of chitosan, which can be effectively applied for mucosal delivery of vaccines as a form of the microparticulate system. In an aqueous environment, chitosan swells and forms a gellike layer, favorable for the interaction of polymers with glycoprotein in mucous. In the case of nasal delivery, chitosan possesses good bioadhesive properties and can reduce the rapid clearance of vaccine from the nasal cavity where it could be delivered to nasal-associated lymphoid tissue – the induction and effector sites for vaccine-induced immune responses.11 General aspects of chitin and chitosan Chitin is an abundant source of chitosan, a unique cationic polysaccharide superior to any man-made cationic derivatives.12 In general, it comprises the skeletal materials in invertebrates. It is also found in egg shells of nematodes and rotifer as well as in the cuticles of arthropods, exoskeletons, peritrophic membranes, and cocoons of insects. In the fungal walls, chitin varies in crystallinity, degree of covalent bonding to other wall components, and DD.12 It was reported as the principal component of protective cuticles of crustaceans such as crabs, shrimps, prawns, and lobsters.11 Chitosan, a natural linear polyaminosaccharide obtained by alkaline deacetylation of chitin, is the second most abundant polysaccharide next to cellulose.12 It is made up of copolymers of glucosamine and N-acetyl-glucosamine, while chitin is a straight homopolymer composed of β-(1, 4)-linked N-acetyl-glucosamine units.13–15 Chitosan has one primary amino and two free hydroxyl groups for each C6 building unit (Figure 1). Due to the presence of abundant amino groups, chitosan carries a positive charge and thus reacts with negatively charged polymers as well as with mucosal surfaces, making it a useful polymer for mucosal delivery.11 Many studies have reported the use of (...truncated)