Brazilian researchers have developed a hydrogel-type polymeric material that could help surmount one of the main technological challenges faced by the pharmaceutical industry today: creating a controlled release system that simultaneously delivers two different drugs with synergistic or combined effects.
In a study supported by FAPESP and published in Applied Bio Materials, a journal of the American Chemical Society (ACS), scientists affiliated with the University of Franca (UNIFRAN) in São Paulo State and Minas Gerais State University (UEMG) tested the use of a class of nanometric materials known as urea siloxane polymer hybrids, or ureasils, for controlled simultaneous release of an anti-inflammatory drug and a cancer drug. The two drugs used in the study have different degrees of water affinity as well as different therapeutic actions.
“We succeeded in designing a system that can simultaneously release two drugs embedded in the same polymeric [plastic] matrix,” Eduardo Ferreira Molina, a professor at UNIFRAN and principal investigator for the project, told Agência FAPESP.
Flexible and transparent, the polymer matrix consists of nanometric segments of siloxane and polyethylene oxide (PEO) to form a hydrogel. Hydrogels are rigid three-dimensional hydrophilic polymer networks that can absorb large amounts of water without dissolving and are therefore widely used in controlled-release drug delivery.
The researchers were able to load the matrix with the anti-inflammatory drug naproxen and the cancer drug 5-fluorouracil simultaneously by using the sol-gel process, in which a liquid with nanoparticles in suspension (a colloidal solution or sol) is gradually transformed into a gel of liquid particles dispersed in a solid medium.
“The idea was to incorporate two therapeutic agents without altering their physicochemical properties or those of the polymeric matrix,” Molina explained.
Naproxen is hydrophobic, whereas 5-fluorouracil is hydrophilic; however, it was possible to incorporate both into the PEO matrix thanks to the functional groups present in the material.
“This enabled us to ‘solubilize’ naproxen and 5-fluorouracil,” Molina said.
In vitro assays to test and measure drug release entailed immersing the material in water with a temperature and pH (acidity) similar to those of the human intestine.
The amount of each drug released into the solution was measured by ultraviolet-visible spectroscopy. The results showed that the material was capable of releasing the two drugs in equal amounts and of sustaining their release over time.
“These findings are unprecedented,” Molina said. “Hitherto, there had been no reports in the scientific literature of any application of this class of material for the controlled release of two drugs simultaneously and in the same amounts for a given period of time.”
Synergistic effect against cancer
According to Molina, the material can be used in multidrug loading for combination chemotherapy, among other applications. Cancer chemoresistance can be delayed by drug delivery systems, such as the one described in the article, which can also improve the effectiveness and mitigate the side effects of the drugs involved.
This effect is because the simultaneous delivery of two drugs tends to promote a synergistic or combined effect, Molina explained.
“In addition to combating cancer, a controlled-release system such as this one containing a chemotherapy drug and another therapeutic agent can reduce the side-effects of the treatment,” he said.
The study also received funding from FAPESP via a master’s scholarship.
The article “Ureasil organic-inorganic hybrid as a potential carrier for combined delivery of anti-inflammatory and anti-cancer drugs” (DOI: 10.1021/acsabm.8b00798) by Beatriz B. Caravieri, Natana A. M. de Jesus, Lilian K. de Oliveira, Marina D. Araujo, Gabriele P. Andrade and Eduardo F. Molina can be retrieved by subscribers to Applied Bio Materials from pubs.acs.org/doi/10.1021/acsabm.8b00798.
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