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New Biodegradable Polyketals Developed for Drug Delivery
Scientists have developed a new family of biodegradable polyketals for the intracellular delivery and sustained release of drugs targeted for acidic environments, including those of tumors and inflammatory tissues. Researchers from Georgia Institute of Technology (www.gatech.edu, Atlanta, GA), Emory University (Atlanta, GA, www.emory.edu), and the University of Rochester (Rochester, NY, www.rochester.edu) have synthesized the polyketal nanoparticles to hydrolyze into FDA-approved hydrophilic compounds.
“One of the interesting polyketals we’ve made degrades into cyclohexane dimethanol, which is an indirect food additive, and acetone, which is on FDA’s list of generally regarded as safe compounds,” says Niren Murthy, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at George Tech and Emory University. “The polyketals will degrade into almost any aliphatic carbon with two hydroxols on it.”
This process offers significant advantages over the degradations of current polyester-based biomaterials, whose byproducts tend to generate acids that lead to inflammation.
Moreover, current biodegradable polyesters are notoriously slow in their degradation. The process can take months, thereby requiring frequent injections when used to treat chronic illnesses. The newly developed polyketals, however, can hydrolyze in a week,
Some of the polyketals are membrane permeable and can be taken up by cells. When cells take up particles, they naturally move them to a part of the cell with a low pH. A polyketal that goes inside of a cell will degrade in the the acidic environment of the cell and the degradation products such as cyclohexane dimethanol and acetone will then diffuse out of the cell. Therefore there is no accumulation outside of the cell that can cause inflammation.
The polymers were developed using a straightforward acetal exchange reaction process. “It’s normally a reaction used to protect alcohols, but when you make it react with a molecule with two alcohols, it makes this polymer,” says Murthy.
Murthy also explains that the polymer’s hydrolysis rates and mechanical properties can be tailored to modify drug-release rates. “With acute liver failure, you want drug release in one to two days, whereas with arthritis, you want release over one to two months.”
Polyketal-based delivery would be suitable for antioxidants to treat acute liver failure. Murthy also says there is a potential application for protein-based vaccines or protein-based therapeutics such as insulin.
“We’ve already been able to encapsulate proteins in polyketals and we have been able to get beautiful SEM images showing that protein is active,” says Murthy.
The researchers are currently investigating the treatment of chronic and acute inflammatory diseases and hope to start animal studies in three months.