Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma

Abstract

Background: Topical anesthetics are widely used in dermatology and cosmetology to alleviate the pain from nonsurgical cosmetic procedures, while the transdermal drug delivery is limited by the skin barrier. Cold atmospheric plasma (CAP) is a potential approach used for skin pretreatment to enhance transdermal delivery of topical medications.

Aims: To assess the efficacy of CAP as a pretreatment to improve the transdermal delivery of topical anesthetic.

Methods: First, we conducted ex vivo permeation studies on 30 mice with a Franz cell diffusion experiment. CAP irradiations of different intensity and duration were pretreated on the epidermal layer of mice before topical lidocaine applied, with the control group received no pretreatment. The amount of drug penetrated through the skin and drug flux were determined by high-performance liquid chromatography. Then, we treated 3 living mice with CAP followed by application of methylene blue cream (MB) and used skin biopsies to measure penetration depth by microscope. Last, we measured the transepidermal water loss (TEWL) of mouse skin in vivo before and after CAP treatment to observe its effect on the skin barrier function.

Results: In the permeation study, the transdermal flux of lidocaine was enhanced to 1.97 times of the control samples by CAP pretreatment. We also observed that the accumulative amount of lidocaine varied with the duration of the CAP treatment in a biphasic manner. In the MB penetration study, significant amount of MB deposition was observed under the epidermis and deeper parts of the skin after CAP pretreatment compared with the control sample. A sharp increase in TEWL value was observed directly after the CAP treatment, but 30 minutes later, it began to decrease and recovered to baseline in the next 3 hours, indicating that the skin barrier property had been changed reversibly.

Conclusions: Our studies suggested that the transdermal absorption of topical lidocaine can be efficiently and safely enhanced by pretreatment of the skin with CAP. We believe that CAP could be used as an assistance to improve analgesia in dermatology.

Keywords: cold atmospheric plasma; dielectric barrier discharge; lidocaine; methylene blue; topical anesthetics; transdermal drug delivery.