Issue 36, 2023

Designing polymers for cartilage uptake: effects of architecture and molar mass

Abstract

Osteoarthritis (OA) is a progressive disease, involving the progressive breakdown of cartilage, as well as changes to the synovium and bone. There are currently no disease-modifying treatments available clinically. An increasing understanding of the disease pathophysiology is leading to new potential therapeutics, but improved approaches are needed to deliver these drugs, particularly to cartilage tissue, which is avascular and contains a dense matrix of collagens and negatively charged aggrecan proteoglycans. Cationic delivery vehicles have been shown to effectively penetrate cartilage, but these studies have thus far largely focused on proteins or nanoparticles, and the effects of macromolecular architectures have not yet been explored. Described here is the synthesis of a small library of polycations composed of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) with linear, 4-arm, or 8-arm structures and varying degrees of polymerization (DP) by reversible addition fragmentation chain-transfer (RAFT) polymerization. Uptake and retention of the polycations in bovine articular cartilage was assessed. While all polycations penetrated cartilage, uptake and retention generally increased with DP before decreasing for the highest DP. In addition, uptake and retention were higher for the linear polycations compared to the 4-arm and 8-arm polycations. In general, the polycations were well tolerated by bovine chondrocytes, but the highest DP polycations imparted greater cytotoxicity. Overall, this study reveals that linear polymer architectures may be more favorable for binding to the cartilage matrix and that the DP can be tuned to maximize uptake while minimizing cytotoxicity.

Graphical abstract: Designing polymers for cartilage uptake: effects of architecture and molar mass

Supplementary files

Article information

Article type
Paper
Submitted
23 Jun 2023
Accepted
29 Aug 2023
First published
30 Aug 2023

J. Mater. Chem. B, 2023,11, 8804-8816

Designing polymers for cartilage uptake: effects of architecture and molar mass

J. Gong, J. Nhan, J. St-Pierre and E. R. Gillies, J. Mater. Chem. B, 2023, 11, 8804 DOI: 10.1039/D3TB01417G

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