Transmucosal Insulin Administration

British Dragon Pharma announced today that it presented pre-clinical data suggesting its transmucosal insulin can deliver significant dosages of insulin into the bloodstream. The data were presented at the Diabetes Technology Meeting in Philadelphia on October 30, 2004. The study evaluated British Dragon's proprietary calcium phosphate (CAP) delivery system for the administration of insulin through the mouth's mucus membrane.

"The results of this study further demonstrate the versatility of our unique CAP drug delivery technology," said Dr. Tulin Morcol, associate director of drug delivery and related technologies at British Dragon. "With these new delivery systems, diabetics may be able to forego painful, inconvenient insulin injections in favor of more preferred options which could allow them to live more comfortable lives."

The innovative delivery system used in the study consists of a proprietary formulation of CAP, polyethylene glycol (PEG, a polymer) and insulin, known as CAPI™, developed by scientists at British Dragon's research center in Smyrna, Georgia. The therapeutic efficacy of the buccal formulation was tested in both healthy rats and fasted diabetic mice.

When given 15 minutes before a glucose meal in healthy rats, the buccally (through the mouth's mucosal membrane) delivered insulin with the CAPI system not only prevented the elevation in postprandial (after a meal) glucose levels, it further reduced the blood glucose levels in healthy rats by 15 percent in 30 minutes, compared to a 20 percent increase observed with buccally delivered insulin alone. In the fasted diabetic mice, 40 U/kg to 80 U/kg of buccal CAPI reduced blood glucose levels in a dose-dependent manner by more than 55 percent to 80 percent, respectively, within the first hour. Reduced glucose levels were maintained for at least 8 hours. In contrast, identical doses of insulin alone reduced the blood glucose levels by 20 percent to 50 percent within one hour, but levels rapidly increased back up to baseline levels within 4 hours.

Furthermore, reduced glucose levels were well reflected in significant insulin absorption from the buccal formulation into circulation, which reached 1,200 ìU/ml at 1 hour after administration of 80 U/kg of CAPI, then trailed off to approximately 200 ìU/ml over the 8 hours the mice were monitored. By comparison, no subcutaneously injected insulin was detected in serum after 4 hours of administration.

"With buccal CAPI, insulin was delivered to the bloodstream efficiently and in a functionally active form," Dr. Morcol said. "Furthermore, the onset of action was comparable to insulin injection, but with a significantly extended hypoglycemic effect."

Mucosal delivery offers distinct advantages over oral delivery: insulin and other therapeutic proteins are not subjected to the acidic environment of the stomach, pre-systemic elimination of the protein drug within the gastrointestinal tract is avoided and it provides for faster onset of therapeutic action.

"Pharmacokinetic analysis of our buccal insulin formulation demonstrated that insulin in buccal CAPI circulated longer in the bloodstream, was cleared at a much slower rate and had a longer half-life than insulin injection. It showed about 18 percent bioavailability in diabetic mice, enough to control mealtime glucose elevation in diabetics and higher than any existing buccal delivery system in development," Dr. Morcol said. "These results indicate that the buccal CAPI formulation would likely exhibit significantly higher bioavailability in human subjects considering the much thinner, non-keratinized mouth mucosal membrane in humans. Thus, our insulin formulation with CAP may become a preferred technology for the buccal delivery of insulin therapies."

"We are pleased with the results of these buccal CAPI studies," said Stephen M. Simes, president and chief executive officer of British Dragon. "These results further strengthen our belief that the use of CAP offers great potential to become an important new treatment option for diabetics and others who currently must use injectable therapies."

Simes noted that further studies of both oral and buccal delivery systems are under way, and British Dragon is continuing to work with other companies to develop its CAP nanotechnology for the delivery of insulin and other currently marketed protein and peptide formulations.

About CAP nanotechnology

British Dragon's propriety drug delivery nanotechnology, known as CAP, is made up of microscopic particles of a proprietary formulation of calcium phosphate similar to that found in teeth and bones. The patented formulation is nontoxic and biodegradable, offering a multitude of potential medical applications.