Thiolated-Chitosan: A Novel Mucoadhesive Polymer for Better-Targeted Drug Delivery

New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan

“…In an acidic environment, chitosan amino groups charge positively [ 31 ] and can thus interact with the negatively charged mucin molecules from the mucous membranes, resulting in mucoadhesive properties ( Figure 2 ) and favoring drug release from the matrix [ 8 ]. Initially, the polymer interacts with the mucosa, and is then deposited on the membrane [ 35 ]. Chitosan inhibits mucociliary development and differentiation by increasing factor TGF-b1 and interferes with the formation of tight junctions in nasal respiratory epithelial cells [ 55 , 56 ].…”

“…The mucoadhesive property of the polymer is directly proportional to the size of the chain and its flexibility; the more flexible the chain is, the easier it is to form a network with the mucus, increasing penetration [ 35 ].…”

“…The positive charge of chitosan is responsible for its application as a permeability enhancer [ 8 ]; the amino and hydroxyl groups form electrostatic interactions with sialic acid present in the nasal mucosa [ 9 , 57 , 58 ]. The amino groups bond ionically with sulfonic acid of the mucus and the amino and hydroxyl groups form hydrogen bonds with the mucus [ 35 ], leading to reversible opening of the tissue junction and the permeation of substances through the nasal epithelium is increased [ 59 , 60 ]. However, the permeation is also improved by prolonging the residence time on the nasal mucosa, due to the mucoadhesive properties of chitosan and, in this way, a better bioavailability is obtained [ 9 , 59 ] through a shorter latency and a faster absorption [ 61 ].…”

“…Toxicity tests for nanoparticles used in nasal immunization based on N , N , N -trimethyl chitosan conjugated to ovalbumin showed that the toxicity in the nasal epithelium and cilia, in rats, is lower compared to other groups, indicating that the use of the polymer in nasal immunization is safer and more effective [ 34 ]. Therefore, it is a suitable polymer for antigen delivery [ 35 ].…”

“…Biomedical investigations on chitosan and its derivatives have been performed due to their properties, including their biocompatibility, biodegradability, non-toxicity, low allergenic activity [ 19 , 20 , 21 , 22 ], mucoadhesion, permeability enhancement [ 23 , 24 , 25 , 26 , 27 ], antibacterial and antifungal properties [ 28 , 29 ], immunogenic character [ 8 , 17 , 30 ], hemostatic properties [ 2 , 8 ], antioxidant activity [ 9 ], and antitumor effect [ 9 , 31 ]. Chitosan has several applications in biomedical and related fields, being used as a matrix for cell development and wound healing [ 8 ] (skin wound healing [ 32 ] and corneal wound healing [ 7 , 33 ]), tissue engineering (bone tissue engineering [ 15 , 34 ], skin tissue engineering, and cartilage tissue engineering [ 35 ]), gene delivery [ 36 , 37 , 38 ], the development of biosensors [ 39 , 40 ], adjuvant for mucosal formulations [ 34 , 41 ], cosmetics [ 42 ], and food packaging [ 43 , 44 ]. It is also a very important component in drug delivery systems [ 9 ] and the delivery of vaccines [ 18 ].…”