SUCCESS IN VIVO: Less than half of the mice receiving nanomedicine treatment were infected with herpes simplex virus, whereas 84 percent of mice given the same concentration of acyclovir using uncoated nanoparticles were infected. Image: Courtesy of Wikimedia Commons
Tears and a runny nose can be unpleasant on a windy day, but these mucosal secretions play a vital role in protecting the body from viruses and other malicious microbes. Unfortunately, mucus is also adept at washing away medication designed to treat infections and inflammation that occur when an infectious agent is successful in penetrating the body's defenses
Knowing that even nanoscale particles of medicine are apt to get caught up in layers of mucus and cleared before they can treat an ailment, a team of Johns Hopkins University scientists has developed specially coated nanoparticles that can penetrate deep into the body's defenses and remain long enough kill harmful microbes. More specifically, the researchers broke down the herpes-fighting drug acyclovir into nanosize units coated with low–molecular weight polyethylene glycol (PEG) and applied them to female mice using a vaginal gel.
The PEG-coated acyclovir particles—about 110 nanometers in size, only slightly larger than a virus—penetrated the cervicovaginal mouse mucus and remained in the vaginal folds there for 24 hours. Less than half of the mice receiving this treatment were infected with herpes simplex virus, whereas 84 percent of mice given the same concentration of acyclovir using uncoated nanoparticles were infected, the researchers reported Wednesday in Science Translational Medicine.
This is the first time the researchers can report a successful nanomedical herpes treatment in living animals, says Justin Hanes, a project researcher and director of the Center for Nanomedicine at the Johns Hopkins University School of Medicine. One of the places where microbicides fail is that they do not fully cover vaginal tissue because the vagina is an organ that has deep folds known as rugae enabling it to expand during childbirth or intercourse, says Hanes, also a co-founder of Kala Pharmaceuticals—a Waltham, Mass.–based company he formed with Massachusetts Institute of Technology Institute Professor Robert Langer to develop mucus-penetrating nanoparticles for treating diseases in the eyes and lungs.
In the reproductive, respiratory and gastrointestinal tracts as well as the sinuses the body clears mucus layers every few minutes. "We needed to design a system that, like some viruses capable of infecting humans at mucosal surfaces, would allow treatment to penetrate deep into the mucus layer where they would not be cleared as rapidly by the body," Hanes says. "Our goal was to coat and line the epithelium with particles [of acyclovir] and then have them stay there with a uniform distribution and release the drug over a longer period of time than you'd have if you administered the treatment in a standard gel preparation that uses uncoated nanoparticles."
"The use of a nanoscale delivery vehicle with [this type of] surface functionality is key to this advance," says Paula Hammond, a chemical engineering professor at M.I.T. Hammond, who did not participate in the Johns Hopkins research, is studying ways to use what she refers to as PEG-coated "stealth" nanoparticles to penetrate and treat cancerous tumors. "The [Johns Hopkins] work shows the relevance of nanomedicine not only for treatment of diseases such as cancer, but for a breadth of other medical applications."
Indeed, Hanes and his colleagues are already targeting their stealthy nanoparticles at several other areas, including eye ailments normally treated with medicated drops as well as the delivery of gene therapy for those suffering from cystic fibrosis. "We have grants to study this for a variety of diseases, including lung cancer and cervical cancer," he says. "We're also trying to develop a similar nanoparticle for a good HIV drug known as tenofovir to see if we can make that drug more effective."