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ODONTOLOGY

Partnership with bees

Propolis gel is being tested for treating the harmful effects of radiation therapy in cases of head and neck cancer

The propolis used in the gel is produced by bees with resins collected from the alecrim-do-campo plant.

Eduardo CesarThe propolis used in the gel is produced by bees with resins collected from the alecrim-do-campo plant.Eduardo Cesar

A drug made ​​from propolis—a kind of resin produced by bees to protect the hive—may help prevent and treat inflammation, infections and mouth ulcers, which are common in patients treated with radiation for cancers of the head and neck region. The gel which adheres to the mucosa of the mouth is being developed by Pharma Nectar, a small company located in Belo Horizonte (Minas Gerais State), in partnership with the Dental School at the Federal University of Minas Gerais (FO-UFMG). It has been tested in vitro, with animals, and has undergone clinical assessments in small groups of people, with good results. It is now being tested on a larger number of patients and being compared with existing drugs for the same type of treatment.

The main types of cancer that affect the neck and head region are those of the mouth, esophagus, larynx and thyroid. According to the National Cancer Institute (INCA), it is estimated that 23,710 new cases of these four types of tumors will be diagnosed in Brazil in 2014. The best treatment is radiation therapy. The problem is that the radiation causes severe side effects, including mucositis (inflammation of the mucosa) and xerostomia (lack of saliva or dry mouth). Furthermore, the radiation alters the microbiota of the mouth, facilitating infections by naturally occurring microorganisms that live there, such as Candida albicans, which causes hoarseness or “frog in the throat.” In patients treated with radiation therapy, the fungus grows uncontrollably, causing a disease called thrush or oral candidiasis. All these changes result in ulcerations and pain. “Some patients are unable to eat or speak and are at risk of developing anorexia and prostration,” says Vagner Rodrigues Santos, an FO-UFMG professor, who is working on development of the propolis gel in partnership with Pharma Nectar.

He says he got the idea in 2007 when he took over coordinating UFMG’s Dental Care Support Project for Patients with Cancer who were Irradiated in the Head and Neck Region. “It was then that I noticed the need for a product that would bring better quality of life to people suffering acutely from xerostomia, mucositis and associated candidiasis,” he says. “The idea occurred to me to create a gel that was mucoadhesive and also had anti-inflammatory, anesthetic, lubricant, antifungal, antibacterial and healing properties—all qualities present in propolis.”

To do this, Santos sought out Pharma Nectar, which specializes in bee products. “The company was loosely established in the early 1980s as a result of our bee initiative in Minas Gerais,” says its executive director, José Alexandre Silva de Abreu. “In 1986 we officially established the company and began to invest in building its physical and financial structure. In 1992, we created Nectar Pharmaceuticals, as we began to focus on pharmaceutical and functional bee products,” says Abreu. “We export to 27 countries and employ 35 people.” In total, there are 86 products in the company’s portfolio.

Questions and consultations
The partnership between Pharma Nectar and FO-UFMG emerged nearly two decades ago. “Shortly after finishing my PhD in oral pathology in 1996, I was looking for a line of research when a colleague happened to mention someone who had treated a fungal infection between the toes with propolis extract,” Santos recalls. “Immediately questions arose: if propolis can treat foot mycosis, can it also treat oral mycosis? Santos then consulted the scientific literature and found there was little research on propolis and infections. “With my first undergraduate internship, I began to investigate the various extracts sold in Belo Horizonte to find out which one was the best inhibitor of the growth of Candida albicans,” he says. “Of the 16 brands we tested, the green propolis from Pharma Nectar gave us the best results for inhibiting the microorganism in vitro.” This propolis is sourced from resins extracted by bees from the alecrim-do-campo plant (Baccharis dracunculifolia), a medicinal plant native to Brazil.

He then began to focus his experiments on this particular propolis; every month he bought samples at the company’s pharmacy. “Until one day Sheila Lemos Abreu, the pharmacist and also a Pharma Nectar partner, asked me why I was buying so much propolis,” Santos recalls. “I told her I was a professor at UFMG and was testing the antimicrobial properties of the extracts in fighting oral infections. We promptly got into a discussion about it and then began to have more frequent meetings on the subject. Pharma Nectar began providing us with samples of raw propolis and extracts.” Using the company’s green propolis and extracts, Santos conducted a series of experiments and developed some products. The studies yielded at least five published papers in scientific journals.

In 2009, Santos sought out Pharma Nectar to develop the gel for exclusive use in cancer patients undergoing radiation therapy treatment. “The idea was that it would replace the battery of drugs that patients use in these cases, such as artificial saliva, anti-inflammatory, antifungal, analgesic, and other drugs, which do not always provide the anticipated effect,” he explained.

“What we have seen so far, both in phase II and phase III of this study, is that patients who use the gel properly before starting radiation therapy do not suffer from mucositis or, if they do, it is not as severe.” Santos says that so far around R$60,000 has been spent on the studies and clinical trials, funded by the Minas Gerais Research Foundation (FAPEMIG).

Scientific article
NORONHA, V. R. A. S. et al. Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis. Current Clinical Pharmacology. fev. 2014. on-line.

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