title: Thiolated chitosans.
abstract: The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. So far, three types of thiolated chitosans have been generated: chitosan-cysteine conjugates, chitosan-thioglycolic acid conjugates and chitosan-4-thio-butyl-amidine conjugates. 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 6--100-fold augmented (I). The permeation of paracellular markers through intestinal mucosa can be enhanced 1.6--3-fold utilizing thiolated instead of unmodified chitosan (II). Moreover, thiolated chitosans display in situ-gelling features, due to the pH-dependent formation of inter- as well as intra-molecular disulfide bonds (III). This latter process provides a strong cohesion and stability of carrier matrices being based on thiolated chitosans (IV). Consequently, thiolated chitosans can guarantee a prolonged controlled release of embedded therapeutic ingredients (V). The potential of thiolated chitosans has meanwhile also been demonstrated in vivo. A significant pharmacological efficacy of 1.3% of orally given salmon calcitonin, for instance, could be achieved utilizing thiolated chitosan as polymeric drug carrier matrix, while no effect was reached using unmodified chitosan. According to these results thiolated chitosans represent a promising new category of polymeric excipients in particular for the non-invasive administration of hydrophilic macromolecules. Further applications such as their use as scaffold materials in tissue engineering or as coating material for stents seem feasible.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: Margit
authors.initials: M
authors.lastname: Hornof
authors.forename: Davide
authors.initials: D
authors.lastname: Guggi
mesh_terms: D000818:Animals; D048271:Chitosan / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005544:Forecasting; D010455:Peptides / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D010455:Peptides; D013438:Sulfhydryl Compounds; D048271:Chitosan