Feasibility of transdermal delivery of Cyclosporine A using plasma discharges

Abstract

A study of the transdermal delivery of Cyclosporine A by atmospheric plasma irradiation was realized on the epidermal layer of the Hairless Yucatan micropig. Drug flux and the amount of drug penetrated through the skin were determined by a Franz cell diffusion experiment. After treatment of the skin by atmospheric plasma jet or microplasma dielectric barrier discharge, an increase in the permeability of the skin was observed. The authors did not observe drug penetration for samples that were not treated with plasma. There was no significant difference between treatments of skin by plasma jet or microplasma dielectric barrier discharge. Drug flux increased to its maximal value up to 3 h after the drug application, and then it decreased. This phenomenon could indicate a temporal effect of plasma on skin. A pharmacokinetic two-compartment model was developed to estimate the possibility of using plasma drug delivery of Cyclosporine A in medical praxis. Our model showed that it is possible to use this technique if a suitable treatment area and concentration of applied drug are chosen.

Plasma Permeabilization of Human Excised Full-Thickness Skin by µs- and ns-pulsed DBD

“…Both the permeabilization of skin as well as the retention of the skin barrier function have been observed for different plasma sources and treatments [9][10][11]. In several studies an improved penetration or permeation of diverse test substances has been achieved; among the diverse test substances were fluorescently labelled dextran molecules [12], cyclosporine A [13], vitamin D [14], and nucleic acids [15]. While we study plasma permeabilization as a method to facilitate drug delivery, depending on the clinical setting, it might also be an unwanted side effect to be avoided.…”

Microplasma Drug Delivery

“…Concentration of Cyclosporine A in blood of adults 55, 70 and 85 kg in weight (400 mg/ml of Cycloporine A in propylene glycol). The two peaks at 6 and 8 h come from experimental data of drug flux containing some errors [13] (reproduced from Ref. [13], with the permission of the American Vacuum Society).…”

“…The two peaks at 6 and 8 h come from experimental data of drug flux containing some errors [13] (reproduced from Ref. [13], with the permission of the American Vacuum Society).…”

“…Argon plasma and microplasma showed Figure 7. Accumulative amount of penetrated Cyclosporine A through the epidermal layer of the pig skin (four samples were used for microplasma dielectric barrier discharge treatment and five samples for plasma jet treatment) [13] (reproduced from Ref. [13], with the permission of the American Vacuum Society).…”

“…The time of plasma application was set up to 2 min in pulsed mode 1-10 μs and frequency ranged from 50 Hz to 3.5 kHz. The delivery of large molecules such as dextran molecules with a molecular weight 10 kDa can penetrate to a depth of 600 μm within 1 h and larger molecules such as albumin (66 kDa), IgG human immunoglobulin (115 kDa) and SiO 2 nanoparticles with a diameter of 50 nm can penetrate to a depth of 200 μm within 1 h. Even liposomes with a diameter of 100 nm were delivered to a depth of 100 μm after 1 h. Remote microplasma or plasma jet in argon gas were investigated for transdermal delivery of galantamine hydrobromide (368 Da) [14] and Cyclosporine A (1200 Da) [13]. After 3 min of microplasma treatment, the permeability of galantamine hydrobromide increased by a factor 2 after 24 h in comparison with non-treated skin.…”