Research could pave the way for injectable gels that release drugs over time

Gels are created by mixing polymers into liquids to create gooey products that are useful for everything from holding hair in place to allowing contact lenses to float over the eye. .

Researchers want to develop gels for health care applications by mixing in medications, and giving injections to patients so that the gel releases the active pharmaceutical ingredient over time. of months to avoid weekly or daily needle sticks.

But standing in the way is a problem that is so easy to understand with the difference between using a hair gel on a beach against blizzards – heat and cold change the character of the gel.

We can make gels with the right properties slowly at room temperature but once we installed them, the body heat would dissipate quickly and the medications would release too quickly. “

Eric Appel, Associate Professor of Materials Science and Engineering

In a paper published on February 2 in the journal Nature Communication, Appel and his team outline in detail their successful first step toward making temperature-resistant, concoction-injectable gels designed to flexibly bend the laws of thermodynamics.

Appel explained the science behind breaking these rules with the equivalent of making Jello: the solid ingredients are poured into water, then heated and stirred to mix well. As the mixture cools, the Jello hardens as the molecules attach to each other. But if the Jello is reheated, the reliquefies will harden.

Jello’s example illustrates the interplay between two thermodynamic concepts – enthalpy, which measures the energy added to or taken from a material, and entropy, which accounts for on how energy changes make a material relatively orderly at the molecular level. Appel and his team had to make Jello a drug that would not melt, thus losing its properties to release time, when the cool body warmed up.

To achieve this, the Stanford team created a gel made of two solid ingredients – polymers and nanoparticles. The polymers were long, like spaghetti that have a natural tendency to stick, and the nanoparticles, just 1/1000th the width of a human hair, stimulated that tendency. The researchers began by dissolving the polymers and granules in separate water and then moving them together. As the commingling agents began to bond, the polymers wrapped tightly around the granules. “This is our molecular Velcro,” said first author Anthony Yu, who did the work as a Stanford graduate student and is now a graduate scholar at MIT.

The strong bond between the polymers and the granules pushed out the trapped water molecules between them, and as more polymers and particles precipitated, the mixture began to glow at room temperature. . Crucially, this gelling process was accomplished without the addition or subtraction of energy. When the researchers exposed this gel to body temperature (37.5 C) it did not like normal gels because the molecular effect of Velcro enabled entropy and enthalpy – order and temperature change, respectively – to stay the level of equilibrium according to thermodynamics.

Appel said it will take more work to make injectable gels, release time safe for human use. While the polymers in these experiments were biodegradable, the grains came from polystyrene, which is commonly used to make fragile knives. His lab is already trying to make these thermodynamically-neutral gels with fully biocompatible components.

If successful, time-released gel could be valuable for administering anti-malarial or anti-HIV medications in areas where there are insufficient facilities where short-term treatments are difficult. -advice currently available for managing.

“We’re trying to make a gel that you could insert with a pin, and then you would have a small blob that slowly melts away for three to six months to provide continuous healing,” he said. Appel. ”This would be a play-off for fighting chronic diseases around the world. “