Iontophoresis, Sonophoresis, and Microneedles Permit Effective Transdermal Delivery of Biologics

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The transdermal delivery of biologics-as well as of conventional drugs-is growing in popularity because the technique offers numerous advantages.

The transdermal delivery of biologics-as well as of conventional drugs-is growing in popularity because the technique offers numerous advantages. It reduces pain, biohazardous waste, and risk of infection. Most importantly, needle-free drug delivery generally increases patient compliance.

At the AAPS National Biotechnology Conference in Boston, held June 19–21, a session entitled “Transdermal Delivery of Proteins,” explored some of the more popular technologies being used today. Among them are iontophoresis, sonophoresis (ultrasound), and microneedles. All of these approaches enhance transdermal drug delivery by increasing skin permeability and allowing the transmission of large molecules.

This is necessary because “99% of a human’s pores are smaller than 100 angstroms in radius,” said Samir Mitragotri, PhD, assistant professor of chemical engineering at the University of California, Santa Barbara ( He points out that with each of these techniques, the drug must penetrate only the upper layer of the epidermis-the stratum corneum, which provides the greatest barrier to transmission.

“Lipid bilayers are the main building blocks of this barrier,” said Mitragotri. “The drug must diffuse through all of the bilayers.”

Mitragotri and the other speakers discussed some of the most common transdermal techniques being used today to penetrate the stratum corneum and deliver life-saving therapeutics.

Iontophoresis propels high concentrations of a charged substance through the skin by a low electrical current. This technique is standard in physical therapy, “but the new thing is using it for systemic delivery,” said Ajay Banga, PhD, professor and chairman of pharmaceutical sciences at Mercer University in Atlanta, Georgia (

Sonophoresis, or ultrasound, creates holes in the skin, and allows fluids to travel into or out of the body. “When sound is emitted at a particular frequency, the sound waves disrupt the lipid bilayers,” said Mitragotri.


He pointed out that the ideal ultrasound frequency range for the transdermal delivery of biologics is 50-60 KHz. “The higher the frequency, the more dispersed the transmission,” he said.

Another technique involves using microneedles to deliver drugs. ”These are extremely small needles that perforate the stratum corneum without stimulating the nerves,” said Mark Prausnitz, PhD, associate professor of chemical and biomolecular engineering at the Georgia Institute of Technology, Atlanta ( They are usually made from solid silicon or metal, and can also be hollow.

Sometimes, microneedles are used with an electronically controlled micropump that delivers the drug at specific times, or upon demand.

Like all of the transdermal methods, microneedles are painless. “Their sensation depends on the geometry of the needle, but length is the most important factor,” said Prausnitz.

Microneedles are also used to extract fluids, such as blood, for measuring glucose.

-Marilyn Kochman