title: In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.
abstract: Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
authors.forename: Gioconda
authors.initials: G
authors.lastname: Millotti
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.forename: Glen
authors.initials: G
authors.lastname: Perera
authors.forename: Claudia
authors.initials: C
authors.lastname: Vigl
authors.forename: Karin
authors.initials: K
authors.lastname: Pickl
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013607:Tablets
chemical_list: D007328:Insulin; D013438:Sulfhydryl Compounds; D013607:Tablets; D048271:Chitosan
keywords: Bioavailability; Polymeric drug delivery systems; chitosan; drug release; in vivo/in vitro corrlations (IVIC); mucoadhesion; oral delivery of insulin in vivo studies; oral drug delivery; solid dosage forms; thiolated chitosan