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|a dc
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|a Byun, Sangwon
|e author
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|a Massachusetts Institute of Technology. Center for Biomedical Engineering
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|a Massachusetts Institute of Technology. Department of Biological Engineering
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|a Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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|a Massachusetts Institute of Technology. Department of Mechanical Engineering
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|a Byun, Sangwon
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|a Frank, Eliot
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|a Grodzinsky, Alan J.
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|a Tortorella, Micky D.
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|a Malfait, Anne-Marie
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|a Fok, Kam
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|a Grodzinsky, Alan J.
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|a Frank, Eliot
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|a Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions
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|b Elsevier,
|c 2015-09-17T17:09:14Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/98536
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|a The availability of therapeutic molecules to targets within cartilage depends on transport through the avascular matrix. We studied equilibrium partitioning and non-equilibrium transport into cartilage of Pf-pep, a 760 Da positively charged peptide inhibitor of the proprotein convertase PACE4. Competitive binding measurements revealed negligible binding of Pf-pep to sites within cartilage. Uptake of Pf-pep depended on glycosaminoglycan charge density, and was consistent with predictions of Donnan equilibrium given the known charge of Pf-pep. In separate transport experiments, the diffusivity of Pf-pep in cartilage was measured to be ~1 × 10[superscript −6] cm[superscript 2]/s, close to other similarly-sized non-binding solutes. These results suggest that small positively charged therapeutics will have a higher concentration within cartilage than in the surrounding synovial fluid, a desired property for local delivery; however, such therapeutics may rapidly diffuse out of cartilage unless there is additional specific binding to intra-tissue substrates that can maintain enhanced intra-tissue concentration for local delivery.
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|a National Institutes of Health (U.S.) (Grant AR45779)
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|a National Institutes of Health (U.S.) (Grant AR33236)
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|a Pfizer Inc.
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|a en_US
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|a Article
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|t Archives of Biochemistry and Biophysics
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