title: Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery.
abstract: In the field of drug delivery to the articular cartilage, it is advantageous to apply artificial tissue models as surrogates of cartilage for investigating drug transport and release properties. In this study, artificial cartilage models consisting of 0.5% (w/v) agarose gel containing 0.5% (w/v) chondroitin sulfate or 0.5% (w/v) hyaluronic acid were developed, and their rheological and morphological properties were characterized. UV imaging was utilized to quantify the transport properties of the following four model compounds in the agarose gel and in the developed artificial cartilage models: H-Ala-β-naphthylamide, H-Lys-Lys-β-naphthylamide, lysozyme, and α-lactalbumin. The obtained results showed that the incorporation of the polyelectrolytes chondroitin sulfate or hyaluronic acid into agarose gel induced a significant reduction in the apparent diffusivities of the cationic model compounds as compared to the pure agarose gel. The decrease in apparent diffusivity of the cationic compounds was not caused by a change in the gel structure since a similar reduction in apparent diffusivity was not observed for the net negatively charged protein α-lactalbumin. The apparent diffusivity of the cationic compounds in the negatively charged hydrogels was highly dependent on the ionic strength, pointing out the importance of electrostatic interactions between the diffusant and the polyelectrolytes. Solution based affinity studies between the model compounds and the two investigated polyelectrolytes further confirmed the electrostatic nature of their interactions. The results obtained from the UV imaging diffusion studies are important for understanding the effect of drug physicochemical properties on the transport in articular cartilage. The extracted information may be useful in the development of hydrogels for in vitro release testing having features resembling the articular cartilage.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Stefania
authors.initials: S
authors.lastname: Baldursdottir
authors.affiliation: Department of Chemistry-NSM, Roskilde University , Universitetsvej 1, DK-4000 Roskilde, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Hvidt
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Larsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Anan
authors.initials: A
authors.lastname: Yaghmur
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Larsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
mesh_terms: D000818:Animals; D032701:Biomimetics; D002358:Cartilage, Articular / Q000737:chemistry*; D002417:Cattle; D002809:Chondroitin Sulfates / Q000737:chemistry; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007768:Lactalbumin / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry; D009281:Naphthalenes / Q000737:chemistry / Q000493:pharmacokinetics*; D012212:Rheology; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D023822:Tissue Engineering
chemical_list: D009281:Naphthalenes; C072587:2-naphthylamide; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D007768:Lactalbumin; D009113:Muramidase
keywords: UV imaging; cartilage mimic; chondroitin sulfate; diffusion; drug delivery; electrostatic interactions; hyaluronic acid; hydrogel; transport