IACS researchers have fabricated a cytidine-based hydrogel that self-assembles in the presence of silver acetate and boronic acid and exhibits antibacterial activity against Gram-negative bacteria. The hydrogel can be used for drug delivery applications by using external stimuli such as mechanical stress or by changing the pH.
Researchers at the Indian Association for the Cultivation of Science (IACS) Kolkata have used a using naturally occurring nucleoside molecule cytidine to self-assemble into a hydrogel in the presence of silver acetate and phenyl boronic acid. The hydrogel possessing i-motif DNA-like structure was found to exhibit antibacterial activity against Gram-negative bacterial strains such as E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and multidrug-resistant Morganella morganii.
While silver is known to have antibacterial property, it may not be used due to its toxicity. But when silver acetate was incorporated in the hydrogel the toxicity was reduced and thus suitable for treating bacterial infections. The hydrogel containing silver acetate was found to be non-toxic to normal kidney epithelial cells and red blood cells.
The research team led by Prof. Jyotirmayee Dash from the School of Chemical Sciences, IACS, found the silver-containing hydrogel was capable of killing E. coli. The hydrogel reduces the cell size of the E. coli and disrupts its cell membrane, leading to leakage of cellular contents. The results of the study were published in the journal ACS Applied Bio Materials.
“The hydrogel can be tuned to change the anti-bacterial activity,” says Prof. Dash. “By changing the boronic acid component used in the hydrogel we can prepare a large number of hydrogels with different bacterial killing properties.”
Drug delivery
Besides being able to self-assemble, the hydrogel exhibited thixotropic property — change from a gel to a sol phase when subjected to mechanical shaking or stirring. When allowed to stand, it returned to its original gel phase. The hydrogel is also pH responsive. While being stable between pH 3 and 6, it becomes unstable at more acidic or alkaline pH.
“So the hydrogel can be used for drug delivery applications by using external stimuli such as mechanical stress or by changing the pH,” says Prof. Dash. The low pH of the gel is also another contributing factor for its intrinsic antibacterial activities.
The researchers loaded the hydrogel with cancer drug doxorubicin and made the gel release the drug by subjecting it to mechanical shearing and changing the pH. “We tested the drug-delivery property and in cellulo activities are currently under progress.