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On Target
Polymeric nanogels aid in more efficient drug delivery
Fingers hold a vial containing a nanogel precursor polymer solution

Thayumanavan’s “drug-loaded nanocarriers” can seek out pathogenic cells and pass by healthy ones. For patients receiving chemotherapeutics and other cytotoxic drugs, the nanogels could translate to a faster, more painless recovery.

Many therapeutic drugs can cause collateral damage to healthy cells—a high price to pay for medical treatments—which is why scientists across the globe are working on drug delivery vehicles that can safely regulate their behavior within the body. UMass Amherst polymer chemist Sankaran “Thai” Thayumanavan is developing innovative delivery systems that could revolutionize the way many drugs, including chemotherapeutics and biologics, are administered.

Thayumanavan and his team have assembled polymers into spherical nanoparticles, or ‘nanogels,’ that encapsulate drug molecules and can navigate the biological system to deliver on-target therapeutic benefit. Key to the innovation was simultaneous control over multiple factors that dictate the versatility of a drug delivery system. The resulting “drug-loaded nanocarriers” can seek out pathogenic cells and pass by healthy ones. For patients receiving chemotherapeutics and other cytotoxic drugs, the nanogels could translate to a faster, more painless recovery.

That’ll really be a tremendous achievement…a difference-maker in people’s lives,” says Thayumanavan.

The core technology is the nanogel’s cross-linked polymer design. Thayumanavan and his team were singularly able to incorporate both inherently “water-loving” and “water-hating” components into the same polymer chain.  This mismatch causes the polymers to organize into spherical water-soluble assemblies that can trap water-insoluble drug molecules.   The so-called “polymer cross-links” keep the drug molecules encapsulated until the nanogel is absorbed by a cell.  The nanogel is guided to diseased cells by ligands that decorate its exterior—molecules that can recognize the abnormally high protein concentrations in these cells. Once absorbed, the drug molecules’ release is triggered by the unique environment within the cell.

Because the polymer chains keep the drug molecules non-covalently enclosed, the nanogel is highly versatile. Any drug can be contained within the structure without any additional chemistry, and Thayumanavan is consulting protein chemists on campus and beyond to investigate ligands that recognize an array of pathogenic protein abnormalities. Thus, Thayumanavan and his team have developed a platform technology that serves as a delivery vehicle for a broad range of treatments.

Thai Thayumanavan, chemistry, in the classroom
“We came up with a new idea of how to assemble these nanogels. There’s a broad range of tunability,” says Thayumanavan.

After months of initial work with protein chemists Jeanne Hardy and Scott Garman on protein delivery, Thayumanavan is moving into the next phase of development: delivering disease relevant proteins for targeted tissues. With help from Lisa Minter and Barbara Osborne (Veterinary and Animal Sciences), he is also working to apply the technology to immunological challenges. Interest in the nanogel is high; Thayumanavan is partnering with members of the pharmaceutical industry and expects that it will soon be put into practice.

Thayumanavan first began developing hydrogels with Department of Defense funding. The project was geared at developing safe, effective doses of opioid-based pain medication for soldiers. Guided by their pain, injured soldiers can intake medication that results in opioid-induced toxicity—a state of respiratory depression that leads to severe hypoventilation. Thayumanavan explains that opioids are limiting in that their therapeutic range is narrow, meaning it is difficult to decipher the ideal dose that is effective and does not push the toxic boundaries. Thayumanavan responded to the challenge by engineering a hydrogel-based delivery system for the controlled release of opioids and opioid antagonists. The system responds to biomarkers in the body triggered by opioid toxicity. When flagged, the hydrogel system stops further opioid absorption, and is also capable of releasing an opioid antidote into the body.

Thayumanavan says that while his work with drug delivery systems is drawing significant attention, he believes that successful translation of new technology into practice happens only with collaboration. As he works with industry, he continues to draw expertise from UMass Amherst researchers across campus — a source he claims is pivotal to realizing our campus’ wide potential.

“The bottom line is we have a good critical mass of people doing complementary work so that we can succeed together,” says Thayumanavan.

Amanda Drane ‘12