Transport of anti-IL-6 antigen binding fragments into cartilage and the effects of injury

Byun, Sangwon; Sinskey, Yunna L; Lu, Yihong C S; Ort, Tatiana; Kavalkovich, Karl; Sivakumar, Pitchumani; Hunziker, Ernst Bruno; Frank, Eliot H; Grodzinsky, Alan J (2013). Transport of anti-IL-6 antigen binding fragments into cartilage and the effects of injury. Archives of biochemistry and biophysics, 532(1), pp. 15-22. Elsevier 10.1016/j.abb.2012.12.020

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The efficacy of biological therapeutics against cartilage degradation in osteoarthritis is restricted by the limited transport of macromolecules through the dense, avascular extracellular matrix. The availability of biologics to cell surface and matrix targets is limited by steric hindrance of the matrix, and the microstructure of matrix itself can be dramatically altered by joint injury and the subsequent inflammatory response. We studied the transport into cartilage of a 48 kDa anti-IL-6 antigen binding fragment (Fab) using an in vitro model of joint injury to quantify the transport of Fab fragments into normal and mechanically injured cartilage. The anti-IL-6 Fab was able to diffuse throughout the depth of the tissue, suggesting that Fab fragments can have the desired property of achieving local delivery to targets within cartilage, unlike full-sized antibodies which are too large to penetrate beyond the cartilage surface. Uptake of the anti-IL-6 Fab was significantly increased following mechanical injury, and an additional increase in uptake was observed in response to combined treatment with TNFα and mechanical injury, a model used to mimic the inflammatory response following joint injury. These results suggest that joint trauma leading to cartilage degradation can further alter the transport of such therapeutics and similar-sized macromolecules.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Osteoporosis
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie

UniBE Contributor:

Hunziker, Ernst Bruno

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0003-9861

Publisher:

Elsevier

Language:

English

Submitter:

Stephanie Schmutz

Date Deposited:

31 Mar 2014 12:06

Last Modified:

07 Jul 2014 09:09

Publisher DOI:

10.1016/j.abb.2012.12.020

PubMed ID:

23333631

URI:

https://boris.unibe.ch/id/eprint/42739

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