**3.3 Iontophoresis**

Iontophoresis does not require physical disruption of the skin's outer barrier. This method uses principles of electrorepulsion (for charged particles) and electroosmosis (for uncharged particles) to act on drug molecule rather than the skin [112]. During this process, a device capable of generating electric current is placed on the skin. When delivering a negatively charged peptide or protein, for example, the battery will build up a strong negative charge on the anode, which is placed in the same area of the skin as the drug molecule. Thus, the anode will drive the negatively charged protein or peptide into the skin due to charge–charge repulsion [115, 116]. It is important to note that the rate of drug release can be controlled easily by this method since the entry of the protein or peptide into the

body is proportional to the current being applied to the skin [114]. Although the system successfully delivers small molecules (e.g., lidocaine), delivery of proteins or peptides via this method is still a work in progress.
