Zero Order


Posted in Uncategorized by Amy Ross on June 7, 2010
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The term hydrogel may be unfamiliar, but you’ve probably encountered its oldest and most successful commercial use: the soft contact lens. In order to understand hydrogels, first it’s necessary to explain a few things about polymers.

Polymers are material composed of long chains of repeating molecules. The molecule chains can be as long as tens of thousands of repeating units.  The properties of the polymer depend on the repeating unit and the circumstances under which it is made.  A variety of materials-plastic, rubber, and nylon to name a few-are made of polymers.

A hydrogel is a type of polymer that is  crosslinked and can absorb water. In crosslinking, the polymer chains  are bound together by another compound at regular intervals, creating a “mesh”. The molecular structure looks kind of like a fishing net:

Hydrogel structure at the molecular level

Hydrogels are useful in drug delivery because a drug placed in the hydrogel will diffuse out when placed in an aqueous environment. The rate of diffusion can be controlled by the mesh size (the size of the space bordered by the polymer chains and crosslinking compounds).

From "Matrix metalloprotease selective peptide substrates cleavage within hydrogel matrices for cancer chemotherapy activation". J. Tauro, B. Lee, S. Lateef, and R. A. Gemeinhart. Peptides, Volume 29, Issue 11 (2008): 1965-1973

The system I’m working with takes this idea one step further. It’s designed to treat glioblastoma multiforme, a particularly nasty form of brain cancer. The hydrogel is implanted at the tumor site at the time of resection. The drug in question is attached  to the polymer via a peptide. The peptide is the cleavage site for the enzyme MMP-2. MMPs are a class of enzymes that are produced in normal cells , but are overproduced in cancer cells. The MMP-2 enters the hydrogel and cleaves the peptide, thereby releasing the drug (see Figure).

My specific project is to demonstrate the MMP-2 actually penetrates the hydrogel, and doesn’t just cleave peptides on the surface. To accomplish this, I’ve made a two layer hydrogel. The bottom layer is polyethylene glycol diacrylate (PEGDA) and includes the MMP cleavable peptide.  The top layer is made of polyacrylamide.  Cells will be placed on the top layer. If the peptide is cleaved, we know that the MMP penetrated through the top layer and diffused through the bottom.

I’ve been working on this project for the past four months. I’ve created and optimized the hydrogel bilayer. In the past month, I’ve started cell experiments. I’m also working on some characterization of the hydrogels.

In the next few entries, I’ll be discussing some of the techniques I’ve been utilizing and challenges I have faced in the course of my research.


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