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

Islam MA, Firdous J, Choi YJ, Yun CH, Cho CS - Int J Nanomedicine (2012)

Bottom Line: This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.

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.

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Representative structure of thiolated chitosan: (A) general structure of thiolated chitosan modified by an –SH group (X: linker) and (B) chitosan-N-acetyl-cysteine (modification of chitosan at the D-glucosamine unit by N-acetyl-cysteine).
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f3-ijn-7-6077: Representative structure of thiolated chitosan: (A) general structure of thiolated chitosan modified by an –SH group (X: linker) and (B) chitosan-N-acetyl-cysteine (modification of chitosan at the D-glucosamine unit by N-acetyl-cysteine).

Mentions: Thiolated polymers (ie, thiomers) have gained considerable attention – especially for vaccine delivery – because they are one of the most promising polymers with multifunctional properties including strong mucoadhesivity, enhanced permeation effects, protection ability, stability, and enhanced bioavailability of drugs.109–114 Among various thiomer-based carriers, thiolated CMs (TCMs) are highly popular because of their strong mucoadhesiveness and ability to control and extend drug release profiles with improved permeation ability.115–119 TCMs can be prepared by immobilizing the thiol-bearing chain on the polymeric backbone of chitosan (Figure 3). The strong mucoadhesivity of TCMs is obtained through the formation of disulfide bonds between the thiol groups of TCMs and cysteine-rich subdomains of mucin glycoproteins at the mucosal surface (Figure 4).120 The permeability through the mucosal surface can be enhanced by using TCMs instead of unmodified CMs. Increased permeability is achieved by opening the tight junction after the inhibition of protein tyrosine phosphatase, a key enzyme involved in the closing process of tight junction.110 Due to the formation of inter- and intramolecular disulfide bonds through TCMs, a compact three-dimensional network is generated which allows controlled drug release and leads to high cohesivity. Moreover, TCMs exhibit a reversible opening of the tight junction, which leads to better permeation effects than unmodified CMs.115,117,120 In the case of first-generation thiomers, thiolated chitosan derivatives are prepared by conjugating thiol-bearing aliphatic ligands to the amino groups of chitosan. For example, N-acetyl-cysteine, 6-mecaptonicotinic acid, thioglycolic acid, glutathione, and 2-iminothiolane are the aliphatic thiol-bearing ligands with functional carboxyl groups which form amide bonds with the amino groups of chitosan by carbodiimide to synthesize the thiomers of chitosan.118,121–125 CMs prepared by these thiomers exhibit strong mucoadhesivity, biocompatibility, and enhanced permeability and absorption after oral and nasal administration.


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

Islam MA, Firdous J, Choi YJ, Yun CH, Cho CS - Int J Nanomedicine (2012)

Representative structure of thiolated chitosan: (A) general structure of thiolated chitosan modified by an –SH group (X: linker) and (B) chitosan-N-acetyl-cysteine (modification of chitosan at the D-glucosamine unit by N-acetyl-cysteine).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526152&req=5

f3-ijn-7-6077: Representative structure of thiolated chitosan: (A) general structure of thiolated chitosan modified by an –SH group (X: linker) and (B) chitosan-N-acetyl-cysteine (modification of chitosan at the D-glucosamine unit by N-acetyl-cysteine).
Mentions: Thiolated polymers (ie, thiomers) have gained considerable attention – especially for vaccine delivery – because they are one of the most promising polymers with multifunctional properties including strong mucoadhesivity, enhanced permeation effects, protection ability, stability, and enhanced bioavailability of drugs.109–114 Among various thiomer-based carriers, thiolated CMs (TCMs) are highly popular because of their strong mucoadhesiveness and ability to control and extend drug release profiles with improved permeation ability.115–119 TCMs can be prepared by immobilizing the thiol-bearing chain on the polymeric backbone of chitosan (Figure 3). The strong mucoadhesivity of TCMs is obtained through the formation of disulfide bonds between the thiol groups of TCMs and cysteine-rich subdomains of mucin glycoproteins at the mucosal surface (Figure 4).120 The permeability through the mucosal surface can be enhanced by using TCMs instead of unmodified CMs. Increased permeability is achieved by opening the tight junction after the inhibition of protein tyrosine phosphatase, a key enzyme involved in the closing process of tight junction.110 Due to the formation of inter- and intramolecular disulfide bonds through TCMs, a compact three-dimensional network is generated which allows controlled drug release and leads to high cohesivity. Moreover, TCMs exhibit a reversible opening of the tight junction, which leads to better permeation effects than unmodified CMs.115,117,120 In the case of first-generation thiomers, thiolated chitosan derivatives are prepared by conjugating thiol-bearing aliphatic ligands to the amino groups of chitosan. For example, N-acetyl-cysteine, 6-mecaptonicotinic acid, thioglycolic acid, glutathione, and 2-iminothiolane are the aliphatic thiol-bearing ligands with functional carboxyl groups which form amide bonds with the amino groups of chitosan by carbodiimide to synthesize the thiomers of chitosan.118,121–125 CMs prepared by these thiomers exhibit strong mucoadhesivity, biocompatibility, and enhanced permeability and absorption after oral and nasal administration.

Bottom Line: This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.

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.

Show MeSH