S. Kalghatgi, A. Juluri, S. Stone, R. Gray
EP Technologies LLC,
Keywords: nanomaterials, drug delivery, transdermal delivery, non-thermal plasma
Summary:Nanoscale drug delivery systems including, but not limited to nanoparticles, liposomes, nanotubes, quantum dots, could potentially revolutionize modern drug delivery systems. Nanomaterials have wide applications in pharmaceutical sciences including their use in drug delivery as well as diagnostic imaging, and biosening. Nanomaterials are attractive because of their large surface to volume ratio that helps to bind, adsorb, and deliver other compounds such as drugs, probes, and proteins together. The nanosize device systems can eventually reach in generally inaccessible areas such as tumor cells and inflamed tissues due to their enhanced permeability. Nanomaterials can enable development of new drug-delivery systems and reformulation of existing drugs to enhance the effectiveness, patent protection, patient-compliance, safety and decreasing the cost of health care. Most nanomaterials are significantly large in size, which prevents their topical delivery without artificially enhancing skin permeation. The only method to deliver these novel nanomaterials is via injection, which limits the distribution in skin and may enhance their propensity to agglomerate. Transdermal drug delivery has many advantages over other traditional methods. It can be applied in a localized, non-invasive way, and has the potential for sustained and controlled release of drugs, and other molecules. In addition, it avoids first-pass metabolism, which reduces the concentration of a drug before it reaches the circulatory system and minimizes complications associated with injections. However, only a small percentage of topically applied compounds can be delivered transdermally due to the skin barrier properties, namely the highly lipophilic stratum corneum (SC). As a result only molecules with a molecular weight of less than 500 Da can be administered percutaneously. In this paper, we demonstrate for the first time the use of ambient air-based non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma for enhancing transdermal delivery of various molecules including nanoparticles, liposomes, and proteins across ex vivo porcine skin. We present non-thermal plasma as an alternative technology for non-contact, non-invasive, needle-free and potentially cost effective application that would revolutionize transdermal drug delivery. The objective of this work is to determine the feasibility of non-thermal DBD plasma to enhance skin permeation and transdermal drug delivery especially of nanomaterials including nanoparticles and liposomes without causing any thermal damage. We have demonstrated that non-thermal plasma enables the transdermal delivery of significantly large molecules across porcine skin within an hour after less than a minute of treatment without causing any skin damage. Large molecules including dextrans, nanoparticles, liposomes and proteins were delivered. We propose that the mechanism of plasma-enabled transdermal delivery is the formation of new aqueous pores in the stratum corneum via a reversible ‘plasmaporation’ process. The depth of permeation and drug concentration can be tuned by controlling various electrical plasma parameters. Non-thermal plasma-enabled skin poration provides a non-invasive, safe means for transdermal delivery and cellular uptake of nanomaterials drugs and vaccines at room temperature and atmospheric pressure without the pain, skin irritation and other side effects associated with electroporation and other methods.