If a potentially powerful antibiotic agent is being kept off the market, there must be a good reason; in the case of marinomycin A, it is the result of a frustrating flaw. Derived from a species of marine bacteria, it represents a family of macrodiolides — macrocyclic ethers with some potent medicinal qualities, in this case even an ability to defeat infection from the much-feared methicillin-resistant Staphlococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF).

Unfortunately, marinomycin turns out to be light sensitive, so much so that its delicate polymer structure is hopelessly smashed in less than two minutes’ exposure to direct UV light, which makes it challenging to use in a conventional clinical setting. For Queen’s University chemistry Professor P. Andrew Evans, who led the team that synthesized this important lead in 2012, that might have been the end of the story. Then he met Grahame Mackenzie at the University of Hull, who had developed a technique for replacing the contents of plant spores with active agents, which offers a more effective means of drug delivery. Evans raised the question of whether this kind of microscopic packaging would protect marinomycin from light so that patients could consume it like any other pharmaceutical.

Lycopodium clavatum, a form of clubmoss, grows all around the world.
Credit: Wikimedia Commons

Subsequent research in collaboration with organic chemist Rebecca Goss, a professor at the University of St. Andrews, demonstrated this strategy can work, with the antibiotics being contained in sporopollenin exine capsules derived from Lycopodium clavatum, a type of clubmoss that is found around the world. Evans and his colleagues published their findings earlier this year in the Royal Society of Chemistry journal Chemical Science.

“If you dry the spores, then it’s almost indefinitely stable, which is really amazing,” he explains, noting that the marinomycin remains entirely viable. “Remarkably, marinomycin goes from decomposing within 90 seconds to being stable for more than seven hours in direct UV light, which is significantly stronger than regular sunlight.”

Evans adds that because the spores are naturally occurring, they will not further complicate the approval process for marinomycin, which can be submitted for clinical trials entirely on its own merits. Nor is this approach limited to one particular type of spore-bearing plant; others could be employed to accommodate the features of other agents that were being sequestered in this same way.

“Different plants species give different pore sizes,” he says. “You can tailor the pore size to the size of molecule, which makes this a fairly versatile strategy.”

Given the potential for light to ruin this production method, the work also considered the viability of a fermentation process that could enable encapsulation to take place in the dark. Evans expressed his admiration for the dedicated work of Christopher Bailey, a doctoral candidate in the Goss lab at St Andrews, who pursued this question and spent several challenging months working with marinomycin under lightless conditions.

In the meantime, he has also heard from representatives of pharmaceutical firms who have indicated that their libraries include a variety of other drug candidates which, like marinomycin, fell short of practical clinical implementation. Some of these could well be brought to market through this same form of encapsulation.