Novel research has recently come to light with a new study published by the International Journal of Pharmaceutics, which has outlined the innovative development of an oral anticancer drug, 5-Fluorouracil.
Study: The development of a novel oral 5-Fluorouracil in-situ gelling nanosuspension to potentiate the anticancer activity against colorectal cancer cells. Image Credit: Kateryna Kon/Shutterstock.com
The oral use of this anticancer drug has previously been rejected by the United States Food and Drug Administration (FDA), with the intravenous and topical routes being approved and preferred. However, this novel research illustrates the advancement of the oral route of the drug against colorectal cancer cells.
Why Oral Drug Administration Routes May Be Effective
Colorectal cancer (CRC) is one of the most common types of cancers, with a high incidence rate, especially in the United States. The treatment for this cancer type includes chemotherapy and the single-agent regimen of 5-Fluorouracil (FU), and this can be problematic as the plasma half-life of this drug is approximately 16 minutes after intravenous administration.
The advice that aims to solve FU's short half-life issue is a recommendation of increasing the frequency of doses or intravenous administrations; however, this avenue can cause adverse effects and result in low compliance. Additionally, the intravenous administration of this drug can lead to systemic cytotoxicity due to poor selectivity and an inability to target cancer cells.
The oral route of administering FU can have both benefits and drawbacks, with advantages such as rapid gastrointestinal absorption and maximum plasma concentration being produced between 15 and 60 minutes. However, the disadvantages of this administration method include FU being converted to polar metabolites during gastric metabolism, resulting in slower absorption rates, causing adverse effects, and even reducing efficacy, with low selectivity for cancer cells.
With the potentiality of oral administration, innovative researchers have developed a method in order to design a delivery system that sought to prolong or minimize the gastric retention time to increase the efficacy. This would also aim to solve the concerns from the FDA about oral drug administration leading to erratic absorption from the gastrointestinal tract.
Innovative Drug Delivery Systems
Existing literature has investigated the use of polysaccharides for drug delivery systems previously, with sodium alginate, carrageenan and chitosan being explored as methods to modify the release of the drug and increase the pharmaceutical benefits of FU.
Sodium alginate has been attributed to having a gelling ability and so has been previously used as a primary carrying vehicle.
Carrageenan is considered to be a polysaccharide isolated from Irish moss, previously used for their coating and gelling characteristics that can be used to manipulate the solubility of drugs. When used with safe and effective amounts, sodium alginate and carrageenan have been referred to as immunostimulants with associated anticancer activity.
Additionally, the use of chitosan has been approved to activate the p53 tumor suppressor gene as well as to decrease the adverse effects and immune-incompetence of the anticancer drug FU. It can also increase interferon-gamma levels, a key marker of immune stimulation.
The researchers of this innovative study aimed to enhance the oral sustained-release of anticancer drugs through the development of nano-formulations of FU. They encapsulated the particles within an aqueous hydrodynamic gel of sodium alginate with carrageenan or chitosan, with the optimum suspension being determined through drug release analysis, gel characterization and particle size analysis.
The optimal sustained-release formulation consisted of 20 to 63 nm nanosuspensions with FU nanoparticles being coated with carrageenan and sodium alginate which was tested against colorectal cancer cells to evaluate its efficacy as a potential treatment.
Future Colorectal Cancer Treatment Implications
This research could have potentially significant applications as a long-acting therapy with a possible approval by the FDA for a nanotechnology oral anticancer treatment. This potentially revolutionary therapy with advanced coatings could protect the drug nanoparticles through being pH-selective and having a sustained release matrix, in-situ gel formulation in the stomach and the polymer coating of released drug nanoparticles.
With this type of cancer being the world's fourth most deadly and causing approximately 900,000 deaths annually, the necessity to advance its treatment options is critical. This would reduce the adverse effects of intravenous treatment of FU as well as decrease the mortality and morbidity associated with this very common and severe cancer type.
The incorporation of nanotechnology for a sustained release oral treatment of a chemotherapy drug could be a stepping stone for advancing cancer therapy. This research can also be utilized for other cancer therapies, which could reduce the cancer pandemic for the global population.
Continue reading: Semiconducting Polymer Nanomaterials for Cancer and Tumor Treatment.
Abdullah, S., El Hadad, S. and Aldahlawi, A., (2022) The development of a novel oral 5-Fluorouracil in-situ gelling nanosuspension to potentiate the anticancer activity against colorectal cancer cells. International Journal of Pharmaceutics, 613, p.121406. Available at: https://www.sciencedirect.com/science/article/pii/S0378517321012126
Dekker, E., Tanis, P., Vleugels, J., Kasi, P. and Wallace, M., (2019) Colorectal cancer. The Lancet, 394(10207), pp.1467-1480. Available at: https://doi.org/10.1016/S0140-6736(19)32319-0
Kuipers, E., Grady, W., Lieberman, D., Seufferlein, T., Sung, J., Boelens, P., van de Velde, C. and Watanabe, T., (2015) Colorectal cancer. Nature Reviews Disease Primers, 1(1). Available at: https://doi.org/10.1038/nrdp.2015.65