A team of U.K.- and Spain-based researchers has created a new formulation for two common antibiotics that is designed to be simple and easy to commercialize. The new nanoformulation involves a polymer called alpha-keto polyester that can be bonded to drugs, such as antibiotics.

According to researcher Iris Batalha, PhD, from the Institute for Bioengineering of Catalonia, the polymer is simpler and more versatile than those currently approved for drug formulation.

“I think there is a really big need for improved polymer-drug conjugates,” she explains. “There are a couple of polymers approved, but most have limited sites of conjugation and are not biodegradable.”

Batalha recently presented results at Bioprocessing Summit Europe using the polymer bonded to isoniazid, a first-line antibiotic treatment for tuberculosis. The polymer was also formulated with a surfactant to encapsulate clofazimine, a repurposed drug in clinical trials for tuberculosis treatment.

The team found that the combined nanoformulation worked better at treating Mycobacterium marinum infection—a genetic relative of tuberculosis—in a zebrafish model than giving the drugs on their own, she says.

“Our nanoparticles contained drugs at the same concentration and, not only did they have better therapeutic efficacy, but they also reduced granuloma,” she explains.

Caption: Cryo-EM images of polymeric nanobiotics [Images acquired by Cambridge CryoEM Pharmaceutical Consortium]
Granulomas are clusters of white blood cells and other tissue that form in the lungs after tuberculosis infection. They are typically hard to treat, she says, because the progression of the disease can restrict antibiotic access. Having tested the formulation to see if it works better than existing drugs, Batalha and the team are now adapting it to target specific tissues or diseased cells.

“Nanoparticles have a lot of potential because they can target specific cells, reducing the toxic side effects of therapies that require a combination of several drugs, such as in cancer treatments and hard-to-treat bacterial infections, and increasing the amount of drug that reaches the target tissue while reducing the overall doses given to patients,” she adds.

The polymer nanoformulation, she says, is designed to break down in the acidic environment of cells infected with tuberculosis. The polymer size can also be tuned without affecting the drug loading capacity, as there is one bond per monomeric unit of polymer.

According to Batalha, the latter is one way the formulation is designed to be easy for drug companies to commercialize, as it produces consistent and adjustable results.

“Pharmaceutical companies tend to go for polymers that are easy to get approved, as it’s faster to get to market,” she explains. “The innovation here is the conjugation [bonding] is consistently the same and the polymer is biodegradable, making it easier to get regulatory approval.”

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