It is difficult to think of the mouth as the one organ in the body that is hard to deliver drugs to. After all, it is right there, accessible, open and ready for the task. Oral delivery has been the preferred method of administrating drugs since time immemorial, so what could be so complicated about delivering drugs to the mouth itself?
The problem is that the body identifies the mouth as a tube designed to convey substances onward, rather than holding on to them. When attempting to treat a disease in the oral cavity itself, care to needs to be taken to avoid any of the drug being ingested immediately or washed away by saliva. As a rule, the solution comes in the form of lozenges. But to achieve a consistent dosage of medication in the oral cavity at any given time, a patient has to suck dozens of lozenges throughout the entire day, and this is still no solution for taking medication at nighttime. So in many cases, doctors ultimately treat the mouth just like any other inaccessible organ - they administer a high dosage of a drug orally and wait for it to reach the mouth through the circulation of the blood.
New biopharmaceutical start-up CalCident Activity Ltd. has come up with a solution which, on the face of it, looks quite simple, yet is actually a patented engineering innovation. The company's product is a miniature silicon pocket, about the size of a saccharin tablet, that has thin silicon wires running from it which can inserted in between a patient's teeth to anchor it to a tooth arch. The silicon pocket contains a capsule with the drug that is to be released gradually into the oral cavity. "The mouth is quite adaptive," says dentist Dr. Erella Pines, the inventor of the product. "If you hold a small object in your mouth for a number of hours, at some point you get used to it and don't feel it anymore."
"We designed the product so that it can be easily placed in the mouth, even by someone who is ill, using one hand," says CalCident CEO Amnon Engelberg. Another important element is the design of the material that pocket is made from. The silicon is selectively perforated, enabling the drug to trickle out gradually. "We control the rate of release, by controlling both the rate at which the drug is dissolved by the saliva, and the rate at which it trickles out of the pocket through the holes," says Engelberg. The rate of release can be adjusted according to the severity and nature of the disease, the patient's age, size of oral cavity and others.
Not just drugs
CalCident was co-founded by Pines, a dentist by profession and also an operating theater nurse, and Dr. Yoram Sela, currently VP R&D at nutritional solutions company LycoRed Ltd., and formerly director of drug delivery at Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA; TASE: TEVA). Engelberg previously served as CEO of former Elbit Systems (Nasdaq: ESLT; TASE: ESLT) subsidiary Eltan Communications (which was sold to its employees in 1997), and biomed companies Nobesity Ltd., Saliwizer, and PhyMag. The company was established in 2004 under the auspices of the Yozmot Granot Initiative Center, and it recently completed its third year in the incubator. It has also conducted a clinical trial which showed that its product can enrich the concentration of ionized calcium in saliva by 25% more than other solutions. Engelberg estimates that the company will need another $2 million for the next two years. He and Pines believe they will be able continue from that point onwards through strategic collaborations with drug companies.
The first product that CalCident is launching was also the one that inspired Pines to invent the silicon pocket. "The enamel layer that coats the teeth gets damaged when the oral environment is acidic, and calcium ions are drawn out from the enamel into the oral cavity. It is known that they won't come out if there already is an ionized calcium environment in the oral cavity," she says. Most of us are familiar with acidity in the mouth from the advertisements for chewing gum - when we chew gum, saliva is secreted, and acid levels in the mouth fall, but what happens if you don't chew gum?
CalCident's first product will secrete both calcium and fluoride. Says Pines, "When I was at dental school, we discussed the problem of calcium deficiency in the teeth. I asked what would happen if we released calcium into the mouth through an infusion drip. This was actually what gave me the inspiration for the product."
CalCident's next product will already be a proper drug for the treatment of oral thrush. Most of us don't know how serious oral thrush is; however, patients suffering from diseases of the immune system, such as AIDS, suffer from very painful mouth sores, which make it difficult for them to eat and swallow saliva. The treatment is usually, as mentioned earlier, in the form of pills or lozenges. Another solution is patches placed on the gums, but these have to be changed frequently, says Engelberg. Using the silicon pocket is likely to substantially reduce the amount of medication needed to improve treatment.
The pocket is suitable not just for the controlled release of drugs, but also as a breath freshener, for the release of nicotine for people trying to quit smoking, or for different types of food additives, for example.
A bigger and more distant dream on which the company still declines to elaborate, is to use its product for controlled drug release not only in cases involving disease in the oral cavity but also diseases of the upper digestive system, and even diseases that do not affect the digestive system but which require a constant preset level of medication in the patient's blood. "Because we're a start-up, we have to stay focused," says Engelberg. "You also need to know what you're not suitable for - in our case, for instance, we are quite definitely not a solution for drugs that taste awful."
Published by Globes [online], Israel business news - www.globes-online.com - on June 18, 2008
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