title: Chemical modification of hyaluronic acid for intraoral application.
abstract: This study was aimed to investigate chemical preactivated thiomers for their potential use in mucosal drug delivery. Thiomers--thiolated polymers--are mucoadhesive polymers with sulfhydryl group-bearing side chains. Thiomers are synthesized by covalent attachment of low molecular mass compounds bearing sulfhydryl group to the polymeric backbone of well-established polymers. Hyaluronic acid-cysteine ethyl ester-mercaptonicotinamide conjugates (HA-CYS-MNA) were synthesized by the oxidative S-S coupling of HA-CYS with 6-MNA. Conjugates were compressed into test discs to investigate cohesive properties, cytotoxicity assays, and mucoadhesion studies. Because of the immobilization of MNA, the HA-CYS-MNA conjugates exhibit comparatively higher swelling properties and cohesive properties corresponding unmodified HA. On the rotating cylinder, discs based on HA-CYS-MNA conjugates displayed fourfold improved mucoadhesion time compared with thiolated polymers. Tensile study results were found in good agreement with rotating cylinder results. Moreover, preactivated thiomers showed higher stability. All polymers were found nontoxic over Caco-2 cells. On the basis of achieved results, the preactivated thiomeric therapeutic agent seems to represent a promising generation of mucoadhesive polymers that are safe to use for a prolonged residence time to target the mucosa requested for intraoral application.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.forename: Julia
authors.initials: J
authors.lastname: Röggla
authors.forename: Muneeb Ahmad
authors.initials: MA
authors.lastname: Idrees
authors.forename: Julia
authors.initials: J
authors.lastname: Griessinger
mesh_terms: D018938:Caco-2 Cells; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009061:Mouth Mucosa / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D011108:Polymers; D013438:Sulfhydryl Compounds; D009536:Niacinamide; D006820:Hyaluronic Acid; D003545:Cysteine
keywords: biomaterials; buccal; hyaluronic acid; intraoral application; mercaptonicotinamide; mucosal delivery; polymeric drug carrier; polymers; preactivated thiomers; thiomers