Study On Non-Equilibrium Atmospheric Pressure Plasma Jets For Transdermal Drug Delivery

Non-equilibrium atmospheric pressure plasma jet（N-APPJ）may induce many biomedical effects on living organisms and has a wide range of application prospects in the field of biomedicine.Transdermal drug delivery（TDD）is a novel drug administration method,which has many advantages over traditioinal approaches.Existing methods to enhance TDD include chemical penetration enhancers,electroporation,microneedles,etc.Although these methods have made great progress,there are some problems such as skin irritation,low efficiency,high cost,pain,and infection risk,resulting in low patient compliance.N-APPJ has the advantages of like high efficiency,safe,non-contact,portable on TDD applications,which attract lots of interest.However,the researches on enhancing TDD by N-APPJ at home and abroad are still in its infancy,more systematic and in-depth researches on its mechanism are needed.In this study,the macromolecular water-soluble drug was used as model drugs to study the feasibility of N-APPJ in promoting TDD.The mechanisms were analyzed from the aspect of discharge uniformity,reactive oxygen species（ROS）,heat,electric field.It lays a theoretical foundation for the clinical application of plasma-promoted transdermal drug delivery.The main contents of this paper are summarized as follows:1.Research on the discharge characteristics of plasma sources.The discharge characteristics,uniformity and ROS level of the DC power-driven air plasma,helium plasma jet and dielectric barrier discharge（DBD）helium plasma jet used in this study were measured.The results show that the DC air plasma and DC helium plasma jets show non-uniformity on the surface of the grounded conductor,while the DBD helium plasma jet shows uniform surface discharge;the measurement of the absolute density of O atoms shows that the DC air plasma has the highest O density at 7.7×10²² m^-3,which is one order of magnitude higher than the other two kinds of N-APPJs,and the comparison results of the total ROS flux measurement also shows the same trend.2.The effect of discharge uniformity on transdermal drug delivery and its mechanisms.The skin was treated with the three kinds of N-APPJ for TDD experiments.The results show that the inhomogeneous plasma has a stronger enhancing effect.the DC helium plasma has the highest enhancing effect by a factor of 27.5 after 1 min treatment.Combining discharge uniformity,in situ microscopic imaging of skin surface,transepidermal electrical resistance,and tissue sectioning,it is found that non-uniform plasma can produce rapid perforation effect on skin epidermis,while uniform plasma produces mild erosion effect.3.In-vivo Transdermal drug delivery experimental studies.In-vivo insulin transdermal drug delivery was operated on mices,the effect of plasma was estimated by glucose level of mice.The results show that N-APPJ is able to promote the insulin transdermal delivery.4.Research on the effect of reactive oxygen species on transdermal drug delivery.The effects of N-APPJ with different ROS fluxes on transdermal drug delivery were investigated by controlling the oxygen composition in the working gas,voltage parameters and treatment time.The results showed that ROS flux of plasma was positively correlated with the effect of transdermal drug delivery,which suggests that the ROS play a key role in the interaction between plasma and skin;the TDD efficiency can be enhanced up to more than 100 fold by modulating ROS flux.5.Research on the possibility of electroporation effect by plasma.The electric field strength at the surface between N-APPJ and dielectric surface was measured by using electro-optic effect and the value was around 100～120 k V/cm.The electroporation effect was proved by comparing inactivation effect of electric field on bacteria.