Physical enhancement of transdermal drug delivery: Polysaccharide dissolving microneedles and micro thermal skin ablation

Transdermal drug delivery system has sought various methods to administer biopharmaceuticals with the development of the technologies for the production of biopharmaceuticals. Because skin has the intrinsic function to protect the body preventing entry of the external species into the body, the controlled removal of the skin barrier without losing the protection function is the key to the transdermal administration of biopharmaceuticals through the skin.;In this thesis, two physical methods were studied to overcome the skin barrier in the controlled breakage of the skin barrier and to deliver macromolecules-based drugs through the skin; (1) polysaccharide dissolving microneedles and (2) micro thermal skin ablation.;The previous generation of microneedles has demonstrated the enhanced skin permeability to molecules that cannot penetrate stratum corneum, which is the outmost layer of the skin, by breaking it in a micron size. However, many types of microneedles have focused on the controlled breakage of stratum corneum so microneedles material was selected with the good mechanical properties and the capability of the easy processability for the mass production. These criteria for the material limited the encapsulation of biopharmaceuticals within microneedles due to the incompatible properties of them with sensitive biopharmaceuticals. Thus, polysaccharide dissolving microneedles system was designed and developed in this study to encapsulate biopharmaceuticals without losing their integrity, to break the skin barrier in a minimized size with the mechanically poor material, to release them into skin with the dissolution of microneedles, and to deliver human growth hormone into the living hairless rats.;The skin ablation methods have been evolved to administer biopharmaceuticals because it is a simple method to overcome the skin barrier and deliver drugs. Many of them have already shown the effect of the removal of stratum corneum on the skin permeability to macromolecules, but they are somewhat subjective for the practical application or less controlled for the selective removal of the skin barrier leaving the possibility of the deeper skin tissue damage. Thus, micro thermal skin ablation was designed and developed to fabricate the device generating the energy impact with the basis of arc discharge, to transfer the energy impact on the skin, to remove stratum corneum selectively with three-dimensionally controlled manner, and to deliver hydrophilic macromolecules through skin.