A U.S. patent covering drug delivery via eye drops or nasalspray has been issued to Cambridge Biotech Corp. (CBC) ofWorcester, Mass. The company originally developed thesaponin molecules protected by Patent No. 5,273,965 asimmuno-enhancing adjuvants, trademarked Stimulon, to beefup recombinant subunit vaccines. They are under developmentby a number of biotechnology and pharmaceutical companiesin partnership with CBC (see BioWorld, Jan. 26, 1993).
Saponins are soap-like or detergent-like compounds that havethe property of lysing cells, such as erythrocytes in thebloodstream. This side effect turned out to be primary whenthe company's researchers discovered that certain saponinscould "poke temporary holes in mucosal membranes," GeraldBeltz, CBC's vice president of research, told BioWorld.
So far, saponin-bound insulin dripped in the eyes or sprayed inthe noses of diabetic rats "took the animals down tonormoglycemia in minutes," Beltz said. Neither ocular nor nasaltissue showed any signs of irritation, he added.
But before human trials can begin, Beltz and his researchersmust solve some basic problems with their now-patenteddelivery system. "Insulin is our best first application," he said,"but sprayed intranasally, its dose can't be titrated nearly asprecisely as by needle or even by eye drops. We're still tryingto figure out this error range, to determine how much actuallygets delivered."
Meanwhile, he is working closely with Fred Wagner, presidentof BioNebraska Inc., with which CBC has a joint venture forusing recombinant growth hormone releasing factor (GHRF) astherapy for osteoporosis.
The 5-year-old R&D company, based in Lincoln, has ties to theUniversity of Nebraska. Bruce Partridge, a protein chemist atBioNebraska, anticipates that clinical trials will start within sixmonths. GHRF, he explained, controls increased bone growth.Beltz said Wagner is interested in possible administration ofGHRF by eye or nostril once it is at the stage of human use. "It'san application with a lot of potential to get away from theinjectable route of delivery," Beltz said.
So far, the application is practical only for delivering very smallmolecules in the 5,000-10,000 MW range. Most vaccines andtherapeutic proteins are at least 10 times that size and don'tpass through the membrane perforations the saponins make.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.