Researchers from the Indian Institute of Science (IISc) and Institute for Stem Cell Science and Regenerative Medicine (inStem), both from Bengaluru, have developed an insulin-releasing double-brush polymer hydrogel that controls elevated glucose levels in the blood efficiently.
The effects of elevated blood glucose levels or hyperglycemia due to malfunctioning or reduced levels of insulin hormones are very well known. From eternal tiredness to crippling blindness or gangrene, high sugar levels in the blood can play havoc with diabetics. According to WHO, in 2019 alone, the world over, about 42 lakh people died due to diabetes-related complications.
Keeping the blood sugar levels low using insulin, unfortunately, comes at a cost, both the drug and the misery of injection as multiple injections in a day are needed for some. The sustained release gel could be a boon for such unfortunate patients.
As an alternative to injections, tiny microcapsules of natural jelly-like chitosan or alginate, micelles or tiny fat bags containing insulin and other methods have been tried before to get the drug into the body and release it slowly. They are not without problems. Alginate and chitosan gels can carry only a limited amount of drug weight by weight, while others carrying heavier loads of insulin fail to release it as fast as the body needs. As a result, sustained release of insulin for up to only seven days has been possible. The IISc-inStem effort aims to better this using ingenious chemistry.
S Ramakrishnan, a professor of IISc and Praveen Kumar Vemula, an associate professor at inStem, along with their teams, have created a polymer gel which, besides carrying heavy loads of insulin, also lets go of it easily once inside the body. They use “double brush polymers” to do the trick.
Double brush polymers are long chain molecules that carry hydrophilic (water-loving) segments on one side of the chain and hydrophobic (water-disliking) segments on the other; such an architecture is shown to form gels when dissolved in water, even at very low concentrations.
By carrying out extensive studies, this gelation was ascribed to the crystallisation of the hydrophobic alkyl segments, whose melting temperature can be tuned to occur between 40-50 degrees Celsius. "Thus, simple warming the hydrogel to such relatively benign temperatures transforms it into a sol, which in turn permits the encapsulation of insulin without losing its activity," explains Ramakrishnan.
The gel was tested in mice with drug-induced diabetes. “A single injection of the insulin-loaded hydrogel efficiently controlled hyperglycemia for 24 hours, whereas 5 repeated injections of free-insulin are required to achieve a similar level of control,” write the authors.
"It showed 90 days of sustained release in buffer solution. Besides ease of manufacture, the materials used are cost-effective too," says Praveen Vemula. The double brush polymer gel can also carry other drugs or smaller molecules than insulin, and keep releasing them for many weeks. But we may need to wait to get it, as it needs testing in larger animals like pigs before putting it to use in humans.