Fluorescent penetration enhancers for transdermal applications

Abstract

Chemical penetration enhancers are often used to enhance transdermal drug delivery. However, the fundamental mechanisms that govern the interactions between penetration enhancers and skin are not fully understood. Therefore, the goal of this work was to identify naturally fluorescent penetration enhancers (FPEs) in order to utilize well-established fluorescence techniques to directly study the behavior of FPEs within skin. In this study, 12 fluorescent molecules with amphiphilic characteristics were evaluated as skin penetration enhancers. Eight of the molecules exhibited significant activity as skin penetration enhancers, determined using skin current enhancement ratios. In addition, to illustrate the novel, direct, and non-invasive visualization of the behavior of FPEs within skin, three case studies involving the use of two-photon fluorescence microscopy (TPM) are presented, including visualizing glycerol-mitigated and ultrasound-enhanced FPE skin penetration. Previous TPM studies have indirectly visualized the effect of penetration enhancers on skin by using a fluorescent dye to probe the transdermal pathways of the enhancer. These effects can now be directly visualized and investigated using FPEs. Finally, future studies are proposed for generating FPE design principles. The combination of FPEs with fluorescence techniques represents a useful novel approach for obtaining physical insights on the behavior of penetration enhancers within skin.

Cleansing Formulations That Respect Skin Barrier Integrity

“…The surfactant permeates into SC mainly through intercellular lipid pathway and might have minimal contact with keratin inside corneocyte envelope. This hypothesis is consistent with a recent study on naturally fluorescent penetration enhancers [ 40 ]. The two-photon fluorescence microscopy images of skin treated with a more hydrophobic molecule, sodium sulforhodamine G (SRG), showed that SRG is mostly confined in the cornified envelope and did not penetrate inside the corneocytes.…”

Amino acid derivatives as transdermal permeation enhancers

“…In addition, a significant decrease in skin electrical impedance was found upon the action of L-Pro2. Skin impedance or resistance is often used as a rapid parameter for screening permeation enhancers [58,59] and reflects the skin permeability for ions [60,61]. Thus, L-Pro2 influences different permeation pathways through the skin barrier, which gives it the opportunity to enhance the permeation of a relatively wide range of drugs.…”

A physical mechanism to explain the delivery of chemical penetration enhancers into skin during transdermal sonophoresis — Insight into the observed synergism

“…[9–16] These protocols have been approved by the MIT Committee on Animal Care. Briefly, skin was harvested from the back and flank of Female Yorkshire pigs, sectioned into 25-mm strips, and stored at −85 °C for up to 6 months.…”