When combined with a novel lipid formulation, a natural citrus essential oil from oranges, lemons, and limes—known as limonene—may prove to be effective in relieving xerostomia without significant adverse effects among patients with cancer, according to a recent study published by Wright et al in the International Journal of Pharmaceutics.
Background
Xerostomia—the most reported adverse effect following radiotherapy for head and neck cancer—affects up to 70% of patients as a result of damage to the salivary glands and may lead to difficulty speaking and swallowing, significantly reducing quality of life. “[Patients with cancer] undergoing radiotherapy and other medical treatments regularly experience [xerostomia], which not only prevents them from comfortably swallowing, but can also have other negative and potentially life-threatening outcomes,” explained lead study author Leah Wright, PhD, of the University of South Australia.
Limonene has protective effects on saliva production during radiotherapy, but its poor solubility means that high doses of the oil are needed to take effect, increasing the risk of indigestion, abdominal discomfort, and unpleasant eructation with a citrus taste.
“The therapeutic benefits of limonene are well known. It’s used as an anti-inflammatory, antioxidant, and mood-enhancing agent and can also improve digestion and gut function. [However], despite its widespread use, its volatility and poor solubility have limited its development as an oral therapy,” detailed senior study author Clive Prestidge, PhD, Professor at the University of South Australia. “As limonene is an oil, it forms a film on the top of the stomach contents, causing significant stomach pain and discomfort,” he added.
Study Methods and Results
In this preclinical study, researchers analyzed the efficacy of a lipid-based drug delivery system combined with limonene. Compared with pure limonene, the novel formulation demonstrated 180-fold greater solubility in laboratory experiments and boosted relative bioavailability by more than 4,000% in preclinical trials.
The researchers indicated that the new limonene-lipid combination created a super-solubilizing treatment that reduced xerostomia at a lower dose and without the common adverse effects.
Conclusions
“Our novel formulation combines limonene with healthy fats and oils … to create a super-solubilizing compound that the body can easily absorb with reduced uncomfortable side effects,” Dr. Prestidge highlighted. “This increases the dispersion of limonene in the stomach, boosts absorption, and controls biodistribution—all while increasing a patient’s saliva production and reducing [xerostomia],” he continued.
The researchers suggested that the novel limonene-lipid formulation may have the potential to significantly improve the quality of life among patients with cancer and those experiencing xerostomia.
“While limonene can be ingested directly, it’s not well tolerated, especially by those with [xerostomia]. Plus, its poor absorption prevents it from effectively reaching the salivary glands—the target site,” Dr. Wright underscored. “This inventive and highly impactful limonene-lipid formulation could provide a simple, effective oral solution for [xerostomia], offering patients [with cancer] long-lasting relief and comfort, improved oral health, and a higher quality of life during a difficult time,” she concluded.
The researchers noted that clinical trials for the new formula are ongoing.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.
