Chitosan-based mucosal adjuvants: Sunrise on the ocean

Abstract

Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant.

Natural Vaccine Adjuvants and Immunopotentiators Derived From Plants, Fungi, Marine Organisms, and Insects

“…As an adjuvant, chitosan has a broad number of properties including low manufacturing cost, biocompatibility, low levels of intolerance, and appropriate antibody response (mainly Th1). 56 In addition, it has excellent mucoadhesive properties that make it suitable for vaccines administered via the mucosal route, and it is able to open up tight junctions to enable transport of an antigen to immune effector sites. 57…”

Biodegradable polymers for modern vaccine development

“…Chitosan can induce the redistribution of cytoskeletal F-actin and the tight junction protein zona occludens-1, thus promoting paracellular permeability to hydrophilic macromolecules [95]. The mucoadhesive properties of chitosan prolong the residence time of formulations in mucosa associated lymphoid tissues (MALTs) [96]. Chitosan and its derivatives have been formulated as solutions, gels, powders, and microparticles/NPs to deliver Ags via various routes of administration [97].…”

“…Chitosans are increasingly being used in nanovaccine development [96]. Chitosan-based nanovaccine-DNA NPs are taken up by M cells in MALT [94], and chitosan DNA nanospheres stimulate Th1-dependent cytokine and cytotoxic T lymphocyte (CTL) responses, when co-administered with Ags [99].…”

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“…This polymer is a valuable excipient for delivers therapeutic of peptide, protein, antigen, oligonucleotide and gene 2,17 . Chitosan-based microparticles, as drug delivery systems for proteins or peptides have been extensively investigated for decades, it's find application in a wide range of biomedical uses and was proposed for preparing protein stabilizing matrixes 18 , promotes opening of tight junctions, has strong mucoadhesive properties 15,19 and has been used as mucosal immunoadjuvant and immunopromoter 9,20 .…”