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Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis

Paper ID Volume ID Publish Year Pages File Format Full-Text
6244 468 2014 12 PDF Available
Title
Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis
Abstract

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue's superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (KD ∼ 150 μm) of Avidin to intratissue sites in cartilage. The large effective binding site density (NT ∼ 2920 μm) within cartilage matrix facilitates Avidin's retention, making its structure suitable for particle based drug delivery into cartilage.

Keywords
Cartilage; Post-traumatic osteoarthritis; Size; Charge; Avidin; Drug delivery
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Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 1, January 2014, Pages 538–549
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us