Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery

Research output: Contribution to journalJournal articlepeer-review

Standard

Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics : Implications for Drug Delivery. / Ye, Fengbin; Baldursdottir, Stefania; Hvidt, Søren; Jensen, Henrik; Larsen, Susan W; Yaghmur, Anan; Larsen, Claus ; Østergaard, Jesper.

In: Molecular Pharmaceutics, Vol. 13, No. 3, 07.03.2016, p. 819-28.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Ye, F, Baldursdottir, S, Hvidt, S, Jensen, H, Larsen, SW, Yaghmur, A, Larsen, C & Østergaard, J 2016, 'Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery', Molecular Pharmaceutics, vol. 13, no. 3, pp. 819-28. https://doi.org/10.1021/acs.molpharmaceut.5b00725

APA

Ye, F., Baldursdottir, S., Hvidt, S., Jensen, H., Larsen, S. W., Yaghmur, A., Larsen, C., & Østergaard, J. (2016). Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery. Molecular Pharmaceutics, 13(3), 819-28. https://doi.org/10.1021/acs.molpharmaceut.5b00725

Vancouver

Ye F, Baldursdottir S, Hvidt S, Jensen H, Larsen SW, Yaghmur A et al. Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery. Molecular Pharmaceutics. 2016 Mar 7;13(3):819-28. https://doi.org/10.1021/acs.molpharmaceut.5b00725

Author

Ye, Fengbin ; Baldursdottir, Stefania ; Hvidt, Søren ; Jensen, Henrik ; Larsen, Susan W ; Yaghmur, Anan ; Larsen, Claus ; Østergaard, Jesper. / Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics : Implications for Drug Delivery. In: Molecular Pharmaceutics. 2016 ; Vol. 13, No. 3. pp. 819-28.

Bibtex

@article{4c3a192e1756465591809bd6660b9e2a,
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.",
keywords = "Journal Article, Research Support, Non-U.S. Gov't",
author = "Fengbin Ye and Stefania Baldursdottir and S{\o}ren Hvidt and Henrik Jensen and Larsen, {Susan W} and Anan Yaghmur and Claus Larsen and Jesper {\O}stergaard",
year = "2016",
month = mar,
day = "7",
doi = "10.1021/acs.molpharmaceut.5b00725",
language = "English",
volume = "13",
pages = "819--28",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "3",

}

RIS

TY - JOUR

T1 - Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics

T2 - Implications for Drug Delivery

AU - Ye, Fengbin

AU - Baldursdottir, Stefania

AU - Hvidt, Søren

AU - Jensen, Henrik

AU - Larsen, Susan W

AU - Yaghmur, Anan

AU - Larsen, Claus

AU - Østergaard, Jesper

PY - 2016/3/7

Y1 - 2016/3/7

N2 - 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.

AB - 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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1021/acs.molpharmaceut.5b00725

DO - 10.1021/acs.molpharmaceut.5b00725

M3 - Journal article

C2 - 26808484

VL - 13

SP - 819

EP - 828

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 3

ER -

ID: 169384521