title: Preactivated thiomers for vaginal drug delivery vehicles.
abstract: It was the purpose of this study to design and evaluate a chitosan derivative as mucoadhesive excipient for vaginal drug delivery systems. The chemical modification of chitosan was achieved by conjugation of thioglycolic acid (TGA) resulting in 1594 μmol thiol groups per gram of polymer followed by the linkage of mercaptonicotinic acid (MNA) to the immobilized thiol groups via disulfide bonding leading to 702 μmol ligand per gram of preactivated polymer. The mucoadhesive properties of these polymers within newly designed vaginal formulations (Chitosan-TGA and Chitosan-TGA-MNA) and commercially available vaginal formulations (Candibene®, Daktarin®, Dalacin®, GynoPevaryl®) were tested over a time period of 24 h via a mucoadhesion test system simulating vaginal conditions, tensile studies and mucus polymer interaction studies via viscosity measurements. Within the vaginal test system simulating vaginal in situ conditions, a 1.5-fold increase in mucoadhesion could be observed for preactivated thiomer formulations after 24 h in comparison to commercially available formulations. Similar results were achieved for tensile studies, as the chitosan-TGA-MNA containing formulation resulted in a 4.9-fold increase in total work of adhesion (TWA) in comparison to Candibene which showed the highest TWA value of all tested commercial formulations. Also in terms of rheology investigations of mucus/formulation mixtures, a 5.8-fold increase in dynamic viscosity for chitosan-TGA-MNA containing mixtures could be observed in comparison to the mucus-free control. In contrast, commercially available formulations achieved a maximum enhancement of 1.9-fold. These outcomes confirm that the newly developed polymer is a promising tool for vaginal drug delivery likely providing a prolonged vaginal residence time due to its comparatively high mucoadhesive properties.
authors.affiliation: ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
authors.forename: Heike E
authors.initials: HE
authors.lastname: Friedl
authors.forename: Sarah
authors.initials: S
authors.lastname: Dünnhaupt
authors.forename: Claudia
authors.initials: C
authors.lastname: Waldner
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000282:Administration, Intravaginal; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D011108:Polymers / Q000737:chemistry; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013864:Thioglycolates / Q000737:chemistry; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism; D014783:Viscosity
chemical_list: D005079:Excipients; D011108:Polymers; D013438:Sulfhydryl Compounds; D013864:Thioglycolates; C017487:2-mercaptoacetate; D048271:Chitosan
keywords: Chitosan; Mucosal adhesion; Thiol; Vaginal drug delivery