Synthesis of Thiolated Chitosans: Promising Polymers for Prolonged Mucoadhesive Drug Delivery

The successful development of multifunctional drug delivery systems is mainly based on the development and evaluation of new mucoadhesive polymers. Chitosan is a natural polycationic copolymer consisting of glucosamine and Nacetylglucosamine units. The polymer has valuable properties as a biomaterial because it is considered to be biocompatible, biodegradable and non-toxic. The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. Various properties of chitosan are improved by this immobilization of thiol groups. Due to the formation of disulfide bonds with mucus glycoproteins, the mucoadhesiveness is augumented. The permeation of paracellular markers through mucosa can be enhanced utilizing thiolated instead of unmodified chitosan. Moreover, thiolated chitosans display in situ gelling features, due to the pH dependent formation of interas well as intramolecular disulfide bonds. This latter process provides a strong cohesion and stability of carrier matrices being based on thiolated chitosans and guarantees a prolonged controlled release of embedded therapeutic ingredients.