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Branched poly-l-lysine for cartilage penetrating carriers.

Publication ,  Journal Article
Gonzales, G; Hoque, J; Gilpin, A; Maity, B; Zauscher, S; Varghese, S
Published in: Bioeng Transl Med
May 2024

Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra-articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem is further exacerbated by the dense and negatively charged cartilage extracellular matrix (ECM). Cationic nanocarriers that form reversible electrostatic interactions with the anionic ECM can be an effective approach to overcome the electrostatic barrier presented by cartilage tissue. For an effective therapeutic outcome, the nanocarriers need to penetrate, accumulate, and be retained within the cartilage tissue. Nanocarriers that adhere quickly to cartilage tissue after intra-articular administration, transport through cartilage, and remain within its full thickness are crucial to the therapeutic outcome. To this end, we used ring-opening polymerization to synthesize branched poly(l-lysine) (BPL) cationic nanocarriers with varying numbers of poly(lysine) branches, surface charge, and functional groups, while maintaining similar hydrodynamic diameters. Our results show that the multivalent BPL molecules, including those that are highly branched (i.e., generation two), can readily adhere and transport through the full thickness of cartilage, healthy and degenerated, with prolonged intra-cartilage retention. Intra-articular injection of the BPL molecules in mouse knee joint explants and rat knee joints showed their localization and retention. In summary, this study describes an approach to design nanocarriers with varying charge and abundant functional groups while maintaining similar hydrodynamic diameters to aid the delivery of macromolecules to negatively charged tissues.

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Published In

Bioeng Transl Med

DOI

ISSN

2380-6761

Publication Date

May 2024

Volume

9

Issue

3

Start / End Page

e10612

Location

United States

Related Subject Headings

  • 4004 Chemical engineering
  • 4003 Biomedical engineering
 

Citation

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Gonzales, G., Hoque, J., Gilpin, A., Maity, B., Zauscher, S., & Varghese, S. (2024). Branched poly-l-lysine for cartilage penetrating carriers. Bioeng Transl Med, 9(3), e10612. https://doi.org/10.1002/btm2.10612
Gonzales, Gavin, Jiaul Hoque, Anna Gilpin, Biswanath Maity, Stefan Zauscher, and Shyni Varghese. “Branched poly-l-lysine for cartilage penetrating carriers.Bioeng Transl Med 9, no. 3 (May 2024): e10612. https://doi.org/10.1002/btm2.10612.
Gonzales G, Hoque J, Gilpin A, Maity B, Zauscher S, Varghese S. Branched poly-l-lysine for cartilage penetrating carriers. Bioeng Transl Med. 2024 May;9(3):e10612.
Gonzales, Gavin, et al. “Branched poly-l-lysine for cartilage penetrating carriers.Bioeng Transl Med, vol. 9, no. 3, May 2024, p. e10612. Pubmed, doi:10.1002/btm2.10612.
Gonzales G, Hoque J, Gilpin A, Maity B, Zauscher S, Varghese S. Branched poly-l-lysine for cartilage penetrating carriers. Bioeng Transl Med. 2024 May;9(3):e10612.
Journal cover image

Published In

Bioeng Transl Med

DOI

ISSN

2380-6761

Publication Date

May 2024

Volume

9

Issue

3

Start / End Page

e10612

Location

United States

Related Subject Headings

  • 4004 Chemical engineering
  • 4003 Biomedical engineering