In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load

Tim W.G.M. Spitters, Dimitrios Stamatialis, Audrey Petit, Mike G.W. De Leeuw, Marcel Karperien

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Intra-articular injection of drug depots is considered as a therapeutic strategy for the treatment of osteoarthritis. In this study, we designed an in vitro assay in a previously described bioreactor system to evaluate the uptake of a small molecule drug mimic as a function of drug clearance by the synovium and compressive load. Bromophenol blue (BPB) loaded hydrogels were placed on top of bovine articular cartilage explants and were compressed in a dual flow bioreactor. As a control, BPB was directly injected in the bioreactor compartment mimicking the synovial fluid. Subsequently, diffusion coefficients of the dye were estimated based on Fick's law. Mimicking synovial clearance revealed that dye penetration of BPB when released from a drug delivery system placed on top of a cartilage explant was enhanced compared to direct injection of BPB into a simulated synovial fluid. Furthermore, we show the synergistic effect of the amount of load and the frequency on drug uptake by the cartilage. In the described model, we have shown that, under compressive load, drug delivery from a depot was beneficial over conventional intra-articular drug administration. The assay mimics the complexity of the knee joint in several key aspects, which results in a more close representation of the expected drug outcome. In this study, we have evaluated the penetration of a model small molecule drug into articular cartilage under compressive conditions, and future development will focus on incorporating synovial(-like) fluid, synovium, and bone to increase the predictive potential of the assay further.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalAssay and Drug Development Technologies
Volume17
Issue number4
DOIs
Publication statusPublished - 6 Jun 2019

Fingerprint

Articular Cartilage
Bromphenol Blue
Pharmaceutical Preparations
Synovial Fluid
Bioreactors
Synovial Membrane
Cartilage
Coloring Agents
Intra-Articular Injections
Hydrogels
In Vitro Techniques
Drug Delivery Systems
Knee Joint
Osteoarthritis
Joints
Bone and Bones
Injections
Therapeutics

Keywords

  • bioassay
  • bioreactor
  • drug delivery
  • intra-articular
  • osteoarthritis
  • physically crosslinked hydrogel

Cite this

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title = "In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load",
abstract = "Intra-articular injection of drug depots is considered as a therapeutic strategy for the treatment of osteoarthritis. In this study, we designed an in vitro assay in a previously described bioreactor system to evaluate the uptake of a small molecule drug mimic as a function of drug clearance by the synovium and compressive load. Bromophenol blue (BPB) loaded hydrogels were placed on top of bovine articular cartilage explants and were compressed in a dual flow bioreactor. As a control, BPB was directly injected in the bioreactor compartment mimicking the synovial fluid. Subsequently, diffusion coefficients of the dye were estimated based on Fick's law. Mimicking synovial clearance revealed that dye penetration of BPB when released from a drug delivery system placed on top of a cartilage explant was enhanced compared to direct injection of BPB into a simulated synovial fluid. Furthermore, we show the synergistic effect of the amount of load and the frequency on drug uptake by the cartilage. In the described model, we have shown that, under compressive load, drug delivery from a depot was beneficial over conventional intra-articular drug administration. The assay mimics the complexity of the knee joint in several key aspects, which results in a more close representation of the expected drug outcome. In this study, we have evaluated the penetration of a model small molecule drug into articular cartilage under compressive conditions, and future development will focus on incorporating synovial(-like) fluid, synovium, and bone to increase the predictive potential of the assay further.",
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In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage : Effect of Synovial Clearance and Compressive Load. / Spitters, Tim W.G.M.; Stamatialis, Dimitrios; Petit, Audrey; De Leeuw, Mike G.W.; Karperien, Marcel.

In: Assay and Drug Development Technologies, Vol. 17, No. 4, 06.06.2019, p. 191-200.

Research output: Contribution to journalArticleAcademicpeer-review

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T2 - Effect of Synovial Clearance and Compressive Load

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AU - Stamatialis, Dimitrios

AU - Petit, Audrey

AU - De Leeuw, Mike G.W.

AU - Karperien, Marcel

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