Nanoscience
Needle-Free Inoculation
High-frequency sound waves interact with an emulsion containing polymer, medicament, and fluorescent dye to form spherical nanoparticles, which are then harvested, charged, and applied to foil-backed film. After applying this film to the skin (A), a pulsed electric field opens pores and drives nanoparticles toward the waiting dendritic cells (B). Diagrams not to scale.
Diagrams of nano-pulse patch and images of nanoparticles courtesy of Mark Horenstein and David Sherr
Today’s drug and vaccine delivery methods have their drawbacks. Hypodermic needles can hurt and require high volumes to get good results; patches take a long time to diffuse medications into the bloodstream; and ultrasonic methods can be slow and damaging to the skin. None do the job with great speed and precision. But what if a physician or nurse could place a device on your arm just like Star Trek’s Dr. Bones, and psht!—you’re inoculated?
Now a team of three Boston University researchers is developing an electrostatic nano-pulse method for rapidly delivering vaccines and drugs through the skin and directly into the body’s immune system. Funded in its pilot stage by the Center for Integration of Medicine & Innovative Technology (CIMIT), the team aims to develop a clinical device for the widespread, inexpensive, and hygienic dosing of a broad spectrum of medications and vaccines.
Potential applications include low-cost, needle-free inoculation of mass populations in developing countries; rapid infusion of antidotes to large populations in response to bioterrorism; and painless, instantaneous injection of patients who loath conventional needles.
The idea—conceived by co-principal investigators Mark Horenstein, professor of electrical engineering, and David Sherr, professor of environmental health—is to encapsulate a drug or vaccine inside biodegradable nanoparticles with diameters about the size of skin pores and apply an electrostatic voltage pulse strong enough to drive them through the skin precisely where a fleet of specialized skin cells called dendritic cells are standing by. Acting as sentinels for the immune system, the dendritic cells carry the nanoparticles to lymph nodes, where an immune response is generated.
Mark Horenstein, left, and David Sherr examine a prototype of their nano-pulse patch, which would deliver drug-laden nanoparticles (seen through a scanning electron microscope, above left) through the skin. Fluorescent dye (shown under UV light, above right) helps track the movement of nanoparticles through the body.
Horenstein is developing the electrostatic nano-pulse technique. One of his challenges is to separate the nanoparticles, which tend to cling to one another the way sugar clumps in a jar. Another is to design a device that can drive nanoparticles into the skin with fewer than 50 volts of electricity, the maximum level thought to be safe for human subjects. “Usually when you’re trying to drive particles with this level of force, you need kilovolts, that is, thousands of volts,” says Horenstein. “So it all comes down to designing the right methods and structures to allow you to effectively get these particles through the skin layer.”
Under the supervision of CNN Associate Director Joyce Wong, graduate student Graham Houtchens is producing the nanoparticles from a biodegradable polymer. Using an ultrasonicator probe, he’s encapsulating a fluorescent dye “vaccine” inside the particles so they become green under a microscope’s fluorescent light, thus enabling the investigators to track the path of the vaccine-toting nanoparticles inside the body.
Sherr has developed plans to evaluate the nano-pulse method in laboratory mice by tracking the fluorescent nanoparticles and adjusting the pulse strength. “If we can get the nanoparticles just below the skin at about one-fifth the depth of a typical human hair and into a layer of skin called stratum corneum,” he says, “that layer has a direct line to the lymph node system.” The team will soon embark on a six-month pilot study to test the concept.