Details

Project TitleMethod to Conjugate Therapeutic Agents Directly to Tissue Surfaces
Track Code2007-127
Short Description

Synthetic peptide-polymer conjugates that can be enzymatically coupled to cartilage providing a general means of drug delivery, tissue engineering and repair or bioadhesives administration in a biocompatible process.

#materials #biomedical #therapeutics #drugdelivery

Abstract

NorthwesternSynthetic peptide-polymer conjugates are enzymatically coupled to cartilage under mild conditions through the formation of isopeptide bonds between the peptides and extra cellular matrix (ECM) proteins. The system provides a general means of drug delivery, tissue engineering and repair or bioadhesives administration in a biocompatible process.

A variety of strategies have been employed to chemically couple natural or synthetic molecules to biological surfaces for drug delivery, tissue repair and tissue regeneration. In contrast the present technology employs a general methodology for tissue surface modification employing biological enzyme mediated crosslinking reactions. Tissue transglutaminase (tTG), which catalyzes the crosslinking between lysine and glutamine residues, forming ε-(γ-glutaminyl) lysine isopeptide bonds, provides a vehicle to enzymatically couple synthetic molecules to tissue surfaces under physiologic conditions. Cartilage, which contains tTG and several ECM substrates of tTG, upon treatment with a variety of short synthetic peptides, containing lysine or glutamine residues conjugated with polymers, readily binds to the conjugates under the action of added tTG. Thus lysine conjugates (EO)2-FKG-NH2, (B2K); (PEG)-FKG-NH2, (B72K) and glutamine conjugates (EO)2-GQQQLG-NH2, (B2Q); (PEG)-GQQQLG-NH2, (B72Q) incubated (30 min, 37°C) with cartilage in the presence of tTG showed incorporation on the tissue surface to depths of 8-13 μM (Figure 1, 2). ECM components fibronectin, collagen II, osteonectin and osteropontin all exhibit binding to the conjugates. No surface incorporation occurs in the absence of tTG. The lysine and glutamine peptides employed were rationally designed to afford favorable tTG substrates. Peptide conjugates of hyaluronic acid (FKG-HA) and functionalized hydrocortisone (HC-GFKG) have been similarly incorporated into cartilage surfaces.

 

The minimally invasive administration of tTG and synthetic molecules to other tissue surfaces provides a novel means to deliver a wide range of functional polymers, biomolecules and therapeutic agents.

Figure 1 (a) Image of cartilage treated with B72K peptide without tTG (b) Image of cartilage treated with B2K and tTG showing stained surface bound conjugate (arrows).

Figure 2 Graph comparing the thickness of cartilage surface tissue modified by four peptide conjugates

Bar = 50 μM.

 
TagsMATERIALS: biomedical, THERAPEUTICS: drug delivery
 
Posted DateJul 7, 2011 12:43 PM

Inventor(s)

Phillip Messersmith*

Marsha Ritter-Jones

Applications

Delivery of functional polymers, biomolecules and therapeutic agents

Advantages

  • Facile enzymatic controlled tissue engineering
  • Successful use under mild physiological conditions
  • Decrease need for invasive therapies

Publications

IP Status

Issued US Patent No. 8,426,179

Contact Information

Vara Josyula, PhD

Invention Manager

(p) (847) 491-4456
(e) vara.josyula@northwestern.edu

Files

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2007-127 Fig1 FLintbox.gif None Download