Hydrogels show promise as a new way to deliver drugs more effectively

Many of the most promising new pharmaceutical products entering the drug development process are hydrophobic in nature, that is, they repel water and are therefore difficult to dissolve in order to make them available for use. ‘body. But now, MIT researchers have discovered a more efficient way to process and deliver these drugs, which could make them much more effective.

The new method, which involves initially processing drugs in a liquid solution rather than solid form, is reported in a journal article Advanced healthcare materialswritten by Lucas Attia, MIT graduate student, recent graduate Liang-Hsun Chen Ph.D. and professor of chemical engineering Patrick Doyle.

Currently, much of drug processing is done through a long series of sequential steps, Doyle says. “We think we can streamline the process, but also get better products, by combining these steps and leveraging our understanding of soft matter and self-assembly processes,” he says.

Attia adds that “many small molecule active ingredients are hydrophobic, so they don’t like being in water and have very poor dissolution in water, which leads to their low bioavailability.” Oral administration of these medications, which patients prefer over injections, presents real challenges in getting the product into the patient’s bloodstream. Up to 90% of candidate drug molecules developed by pharmaceutical companies are actually hydrophobic, he says, “so this applies to a broad class of potential drug molecules.”

Another advantage of the new process, he says, is that it should make it easier to combine several different medications into a single pill. “For different types of diseases where you are taking multiple medications at the same time, this type of product can be very important in improving patient compliance,” he adds. Having to take just one pill instead of a handful makes treatment much more likely. that patients will follow their medications. “It’s actually a big problem with these chronic diseases where patients are on very difficult pill regimens, so combination products have been shown to be very helpful.”

One of the keys to the new process is the use of a hydrogel, a type of sponge-like gel that can retain water and hold molecules in place. Current processes for making hydrophobic materials more bioavailable involve mechanically grinding the crystals down to a smaller size, making them easier to dissolve, but this process adds time and cost to the manufacturing process, offers little control over particle size distribution and may actually damage some more delicate drug molecules.

Instead, the new process involves dissolving the drug in a carrier solution and then generating tiny nanodroplets of that carrier dispersed in a polymer solution, a material called nanoemulsion. Then, this nanoemulsion is squeezed using a syringe and gelled into a hydrogel. The hydrogel holds the droplets in place while the carrier evaporates, leaving drug nanocrystals behind. This approach allows precise control of the final crystal size.

The hydrogel, by holding the droplets in place while they dry, prevents them from simply merging together to form lumpy agglomerations of different sizes. Without the hydrogel, the droplets would merge randomly and “you’d have a disaster,” says Doyle. Instead, the new process leaves a batch of perfectly uniform nanoparticles. “This is a very unique and novel way that our group has invented to achieve this type of crystallization and maintain the nanometer size,” he says.

The new process produces a two-part package: a core containing the active molecules, surrounded by a shell, also made of hydrogel, which can control the time between the ingestion of the pill and the release of its contents into the pill. body.

“We have shown that we can achieve very precise control over drug release, both in terms of timing and speed,” says Doyle, the Robert T. Haslam Professor of Chemical Engineering and Research Professor in Singapore. For example, if a drug targets a disease of the small intestine or colon, “we can control the time before the drug release begins, and then achieve a very rapid release once it begins.” Drugs formulated conventionally with mechanical nanomilling, he says, “would have a slow release of the drug.”

This process, says Attia, “is the first approach capable of forming core-shell composite particles and structuring drugs into distinct polymer layers in a single processing step.”

The next steps in process development will involve testing the system on a wide variety of drug molecules, beyond the two representative examples tested so far, Doyle says. Even if they have reason to believe the process is generalizable, he says, “the proof is in the pudding: having the data in hand.”

The dripping process they use, he says, “may be scalable, but there are a lot of details to work out.” But because all the materials they work with have been chosen as already recognized as safe for medical use, the approval process should be straightforward, he says. “It could be implemented in a few years… We don’t worry about all these typical safety hurdles that I think other novel formulations have to overcome, and that can be very costly.”

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news in MIT research, innovation and education.