In an application of green chemistry, researchers reported in the journal Biomaterials (April 2018) the caffeine-catalyzed synthesis of a new class of polymer gels for drug delivery and other biomedical applications. These caffeine-catalyzed gels (CCGs) are easy to make and are customizable in terms of their chemical and physical properties, such as their composition, shape, solvent sensitivity, drug release, and mechanical strength. The gels have potential to be consumed as chewable and easier to swallow drug-delivery systems. They contain a small amount of caffeine but were found to be safe in toxicity tests. See also: Biomedical engineering; Caffeine; Catalysis and catalysts; Citric acid; Drug delivery systems; Gel; Green chemistry; Polymer

Caffeine-catalyzed ring-opening polymerization. Caffeine, a mild base, catalyzes gel formation through the deprotonation of citric acid to form nucleophilic carboxylates, which open and bond with the epoxy rings of the diglycidyl ether functionalized oligomers of PEG [poly(ethylene glycol] and PPO [poly(propylene glycol), also known as polypropylene oxide] to form a polyester gel. Citric acid also functions as a trifunctional crosslinking agent. [A. M. DiCiccio et al., Biomater., 2018 (CC BY 4.0)]

The reagents used in the synthesis consisted of caffeine, citric acid, and di-epoxy functionalized poly(ethylene glycol) and/or poly(propylene glycol). In addition, all of these ingredients were either food grade or from the U.S. Food and Drug Administration’s (FDA’s) Generally Regarded as Safe (GRAS) materials list—that is, biocompatible. The reaction was a one-pot synthesis in which caffeine, citric acid, and the diglycidyl ether monomers were added to a reaction vessel, heated to 70°C, and stirred until the mixture reached the gel point, as seen by a rapid increase in viscosity. The mixture was then poured into molds and placed in an oven at 90°C for 24 hours, at which point all the reagents had reacted into the gel network. See also: Epoxide; Polyester resins

The researchers found that they could vary the chemical and mechanical properties of the gels and the rates at which drugs were released by preparing gels that contained either poly(ethylene glycol), poly(propylene glycol), or combinations of the two in different ratios. For drug-release experiments, two antimalarial drugs—artesunate and piperaquine—were tested. They were added to the polymerization mixture before the reaction was started. The catalyst and reaction conditions did not damage the drugs. Although further testing is required, the researchers expect that the gels should be able to carry additional types of drugs aside from those that were tested.