Caffeine kick for polymer gels

Materials World magazine
1 Jun 2018

New polymer gels, catalysed with caffeine, could be used for drug delivery. Kathryn Allen reports.  

It turns out caffeine doesn’t just speed up tired commuters. The stimulant can also catalyse the formation of polymer materials. 

This is according to a team of researchers from the Massachusetts Institute of Technology (MIT), and Brigham and Women’s Hospital, USA, who used caffeine in the creation of biocompatible gels. These gels could be used in medical applications, including creating new devices, and drug delivery. Drugs administered using these gels could be chewable or easier to swallow than current capsules, the team claims. 

So far, they have loaded the gels with two antimalarial drugs – artesunate and piperaquine – and expect other drugs to be compatible with the method as well. 

Angela DiCiccio, Hardware Engineer at Verily Life Sciences and lead author of the paper, Caffeine-catalyzed gels, told Materials World, ‘Any drug that is stable in the presence of a transesterification reaction [during which an ester, an organic compound, is transformed into another by exchanging molecules with an alcohol] and soluble in the monomer matrix of choice is eligible for incorporation into the caffeine-catalysed gel. While citric acid and polyethylene glycol or polypropylene oxide monomers are highlighted in this publication, this chemistry is applicable to an incredibly diverse set of constituent monomer candidates.’

Green chemistry

Metal catalysts are usually used in the formation of polymer gels, however, they must be removed from the material before it is safe to ingest. DiCiccio explains that polyester gels, for example, are formed using inorganic complexes of metals, including aluminium, chromium, cobalt, tin, titanium, and zinc, with any remaining catalyst extracted using solvents after the gel is formed. 

Therefore, the aim of this project was to create a gel using catalysts and starting materials that were recognised as biocompatible and ingestible by the US Food and Drug Administration standards. The gels produced using this method contained about the same amount of caffeine as a cup of tea. The team also claims to use green chemistry in the process, using naturally sourced materials, and not requiring the use of solvents to remove excess material or by-products. 

No harmful effects were found in four types of human cells or in rats in preliminary safety tests of the gels.

The naturally sourced caffeine, found in tea and coffee plants, acts as a weak base, removing protons from other molecules. The team used it to catalyse the reaction between plant-derived citric acid and polyethylene glycol (PEG). 

DiCiccio said, ‘Caffeine deprotonates the carboxylic acid of the citric acid group, freeing a nucleophilic carboxylate that can ring open an epoxide on the glycidyl monomer and thus form an ester linkage.’ This type of bioresponsive bond is needed to form polyester gels. If drugs are added to this mixture, they will also react, joining the chain of alternating molecules of PEG and citric acid. 

Tailored gels 

Changing the composition of the gel allows the researchers to alter its chemical and mechanical properties, such as strength, surface structure, and the rate at which the drug is released. They created gels containing PEG, polypropylene glycol, and a combination of both. For this study, a constant variable of 10mol% caffeine was used, but this can be changed to achieve certain reaction speeds and properties.

In addition, the surface structure of the gels can be altered by imprinting patterns – for example, mimicking the surface pattern of a lotus leaf that allows it to repel water. If the surface of the gel material is altered, it can affect the speed at which the material moves through the digestive tract. 

Of modifying the gel’s properties, DiCiccio said, ‘The rate at which drugs are released can be tuned by altering the hydrophilic nature of the network and thus the water uptake and swelling. The more hydrophilic the network, the quicker it will uptake a large volume of fluid and release cargo.’ 

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