A team of biomedical engineers from Brown University has developed a new hydrogel-based delivery system that balances the acidic environment in a tumor and greatly enhances the cancer-fighting activity of the chemotherapeutic drug it encapsulates in lab experiments.
The hydrogel system, which is injectable, acts as a buffer to the drug doxorubicin and directly delivers it to malignant tumors, helping to reduce unwanted side effects that occur when the drug isn’t released directly in the targeted site. The researchers say the hydrogel, which was designed to balance pH levels, has the potential to substantially improve chemotherapeutic treatments and reduce the risk of aggressive cancers spreading in the body by neutralizing acid levels in tumors.
In patients with cancer, acidosis increases the likelihood of metastasis, through which the cancer spreads to other parts of the body. It also significantly reduces the effectiveness of chemotherapeutics. For instance, in acidic environments, doxorubicin — one of the current leading chemotherapeutics — goes through what’s known as ion trapping. Essentially, the drug gets trapped by the acidic environment outside the cells and can’t penetrate inside them, which prevents it from killing the cancer cells.
Doxorubicin is toxic and when administered through the current practice of intravenous delivery, it doesn’t discriminate between cancer cells and non-cancerous healthy cells, leading to significant side effects. Compounding these challenges is that there is no current method to directly balance acidic pH levels in cancerous tumors.
Initial lab tests done on breast cancer cells in vitro show that the method works. The hydrogel acts as a buffer and uses the sodium bicarbonate to increase the pH level, which then causes the chemotherapeutic power of doxorubicin in killing the cancer cells to increase by a factor or two to three.
The researchers chose to develop a biocompatible hydrogel as their delivery system because of their growing use and versatility. Hydrogels, for example, are used for manufacturing contact lenses, hygiene products and used for drug release and medical dressings. The hydrogel system that the researcher developed can be stored at 4 degrees Celsius for long terms of time before use, making it convenient for practical medical use.
Next in this line of research, the team hopes to apply its combined pH regulating and therapeutic delivering hydrogel system in pre-clinical settings and go from experiments in test tubes to experiments in animals and eventually progress to human patients.
Zahra Ahmed, Kevin LoGiudice, Gavin Mays, Angelina Schorr, Rachel Rowey, Haisong Yang, Shruti Trivedi, Vikas Srivastava. Increasing Chemotherapeutic Efficacy Using pH-Modulating and Doxorubicin-Releasing Injectable Chitosan-Poly(ethylene glycol) Hydrogels. ACS Applied Materials & Interfaces, 2023; DOI: 10.1021/acsami.3c09733
Brown University. (2023, September 20). New drug delivery system has potential to improve cancer treatments. ScienceDaily. Retrieved September 20, 2023 from www.sciencedaily.com/releases/2023/09/230920152337.htm
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