title: Engineering surface adhered poly(vinyl alcohol) physical hydrogels as enzymatic microreactors.
abstract: In this work, we characterize physical hydrogels based on poly(vinyl alcohol), PVA, as intelligent biointerfaces for surface-mediated drug delivery. Specifically, we assemble microstructured (μS) surface adhered hydrogels via noncryogenic gelation of PVA, namely polymer coagulation using sodium sulfate (Na(2)SO(4)). We present systematic investigation of concentrations of Na(2)SO(4) as a tool of control over assembly of μS PVA hydrogels and quantify polymer losses and retention within the hydrogels. For polymer quantification, we use custom-made PVA with single terminal thiol group in a form of mixed disulfide with Ellman's reagent which provides for a facile UV-vis assay of polymer content in coagulation baths, subsequent washes in physiological buffer, and within the hydrogel phase. Polymer coagulation using varied concentrations of sodium sulfate afforded biointerfaces with controlled elasticity for potential uses in investigating mechano-sensitive effects of mammalian cell culture. For surface mediated drug delivery, we propose a novel concept termed Substrate Mediated Enzyme Prodrug Therapy (SMEPT) and characterize μS PVA hydrogels as reservoirs for enzymatic cargo. Assembled functional interfaces are used as matrices for cell culture and delivery of anticancer drug achieved through administration of a benign prodrug, its conversion into an active therapeutic within the hydrogel phase, and subsequent internalization by adhered hepatic cells. Taken together, the presented data contribute significantly to the development of novel matrices for surface-mediated drug delivery and other biomedical applications.
authors.affiliation: Department of Chemistry, Aarhus University, Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Fejerskov
authors.forename: Bettina E B
authors.initials: BE
authors.lastname: Jensen
authors.forename: Najah B S
authors.initials: NB
authors.lastname: Jensen
authors.forename: Siow-Feng
authors.initials: SF
authors.lastname: Chong
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Zelikin
mesh_terms: D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D004800:Enzymes, Immobilized / Q000378:metabolism; D005966:Glucuronidase / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D013499:Surface Properties; D023822:Tissue Engineering
chemical_list: D004798:Enzymes; D004800:Enzymes, Immobilized; D020100:Hydrogels; D011355:Prodrugs; D013431:Sulfates; C012036:sodium sulfate; D011142:Polyvinyl Alcohol; D005966:Glucuronidase