New Gel Extends Release Half-Life of PEGylated Drugs

Researchers have developed a first-of-its-kind hydrogel for more effective long-term drug delivery that would also reduce side-effects and discomfort for patients. Their proof-of-concept study showed effectiveness of the hydrogel with the hepatitis C drug PEGylated-interferon.

The team of researchers, led by Dr. Motoichi Kurisawa, principal research scientist at the Institute of Bioengineering and Nanotechnology (IBN; Singapore) of Singapore’s Agency for Science, Technology and Research (A*STAR), developed a hydrogel that enables burst-free sustained-release of PEGylated protein drugs. “The new gel from IBN prevents premature drug release in the body. This allows for long-term drug delivery and reduces the side effects from frequent drug administration. We hope that our solution can improve the treatment and well-being of patients suffering from chronic diseases such as hepatitis C,” said Prof. Jackie Y. Ying, IBN executive director.

Standard treatment for chronic hepatitis C infections includes weekly injection of PEGylated interferon. The frequent injections increases patient discomfort, is time-consuming, and can cause depression and fatigue. It has not been possible to use hydrogels to deliver drugs with long-term efficacy because controlling the drug release rate is difficult. Most hydrogels have a porous structure that causes the encapsulated drugs to leak prematurely and be eliminated rapidly from the body.

The team found a way to regulate the release rate and duration by creating a gel with 3-D microscopic structures of the polymer polyethylene glycol (PEG). The microstructures function like “reservoirs” for PEGylated drugs because of the presence of PEG on the drug. This property prevents premature leaking. The drugs will also flow in and out of the many reservoirs in the gel before being released into the body. This property helps slow the drug diffusion rate. Duration of drug action can also be controlled by changing the size of the reservoir microstructures.

The study showed that a one-time administration of the hydrogel containing the PEGylated interferon was as effective as 8 injections of the medication alone, and that drug effect can last up to 2 months. The hydrogels will degrade naturally and be eliminated from the body once the drugs are fully released.

“Our hydrogels can significantly extend the half-life of hepatitis C drugs by up to 10 times longer than current treatment,” said Dr. Kurisawa, “This work improves the therapeutic efficiency of the drugs, while reducing the need for frequent injections.” “I believe that our method can pave the way for more effective and safe treatment of hepatitis C. We are also testing the microstructured gel for the treatment of other chronic diseases besides hepatitis C,” added Dr Kurisawa.

The study, by Bae KH et al., was published online ahead of print June 11, 2015, in the journal Biomaterials.

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Institute of Bioengineering and Nanotechnology
Singapore Agency for Science, Technology and Research (A*STAR)