Something’s cooking in room 468C of Towson University’s Smith Hall. Graduate student Tory Johnson is turning the crank of a pasta machine, producing not traditional pasta but white, waxy sheets that could one day revolutionize the treatment of herpes.
It’s estimated that 80 percent of the population is affected by the virus, which depending on type can cause cold sores, genital lesions or chicken pox and shingles. While there is no cure for herpes, the virus can be suppressed if patients remember to take a daily pill.
But Johnson and her adviser, Barry Margulies, assistant professor of biology, have created a less expensive and more effective way to deliver the medication—a silicone implant that slowly releases acyclovir, a drug approved by the FDA to suppress herpes. The pair filed an application for full patent protection of the drug delivery system in June 2006 "with major assistance from the University of Maryland Biotechnology Institute, in particular from Dr. Robert Powell," says Margulies.
“The beauty of the implant is that you can deliver a lot less drug—about a million-fold less per day than what is needed orally,” Margulies adds. “And you can deliver it right where the virus hides.”
The virus lies dormant in tissue underneath the ear in the trigeminal ganglion. An implant would be inserted behind the ear near the jaw line and release the drug for five years, according to Margulies.
Margulies first became interested in creating an anti-herpes implant in the late 1980s, while working in the MIT lab of the controlled release guru, Dr. Robert Langer. But at the time any implant would be unable to deliver the therapeutic level of the drug required.
“A normal daily dose was around 1 gram per day,” he explains. Implants deliver far less drug—in the range of 0.1 to 100 micrograms per day.
Then in 2003, Margulies realized that advances in anti-herpes medications just might make it possible to use much smaller doses that would still be effective against the virus. That same year, Johnson began her master’s studies at TU with Margulies and became intrigued by the idea of engineering a drug implant.
Johnson chose silicone—the same substance used in the birth control implant, Norplant— as the packaging material that would contain the drug acyclovir. Next she cooked up a way to combine the two substances—using a hand-cranked pasta machine to knead the powdery drug with a wad of the waxy silicone. The pasta machine produced the perfect medicine—a lasagna-sized, drug-filled noodle.
To form the implant, portions of the noodle were then forced through a syringe and needle. What emerged was a potent sliver of an anti-herpes implant 15 millimeters long and 1 millimeter wide, about the width of a toothpick but one-fourth the length.
60 days, Johnson tested to see whether and how much drug would be
released by placing the implants in a buffer solution. The tests
revealed consistent levels of the drug and that the implant was
still releasing it even after the testing period.
Johnson then started a three-month study of the implant in mice infected with herpes simplex I—the virus that causes cold sores. “The first wave of data indicates that the implants work,” she says. Eight of 17 mice in the control group without the implant had recurrent herpes lesions, while only one of the 17 mice with the implant had lesions. "This puts the data in the 99.3 percent confidence interval of showing the right effect," adds Margulies.
Further tests, including human trials, which are beyond the scope of research at TU, are needed before the implant can hit the consumer market. Both Johnson and Margulies hope a drug company will purchase the rights to the implant and conduct those tests.
“If this version of our implant is a clinical hit, the same silicone-acyclovir combinations could be used for treating genital herpes and shingles, both caused by related viruses,” Margulies says. In years to come, he adds, controlled release anti-viral therapy could change the face of treatment for other chronic infections, such as those caused by HIV.