Micro-needles and sonophoresis are two physical methods for enhancing skin permeation for transdermal drug delivery. A solid micro-needle system with vertical vibration was integrated and its effects on transdermal drug delivery were studied. Evan's blue (EB) staining and histological evaluation were performed to reveal the skin morphology and micro-conduits created by vibrating micro-needles. Trans-epidermal water loss (TEWL) and infection studies on rat's skin after vibrating micro-needle treatment were performed to evaluate the safety of the treatment. In vivo insulin delivery and tetramethylpyrazine hydrochloride (TMPH) permeation were carried out to assess the effectiveness of the transdermal drug delivery using the vibrating micro-needle system. The structural integrity of vibrated micro-needles was studied through SEM photos. EB staining observation showed that EB has diffused significantly on the skin surface treated with vibrating micro-needles. The micro-conduits were seen by histological visualization. TEWL values increased significantly after treatment as vibration frequency increased. The infection evaluation showed a slight increase of white blood cell number resulted from vibrating micro-needle treatment. The in vivo insulin absorption experiment demonstrated an enhanced transdermal delivery of insulin through vibrating micro-needles treatment, and the effectiveness of blood glucose level increased with increasing vibration frequency. The TMPH permeation study showed an obvious enhanced skin permeability due to vibrating micro-needle pretreatment. The degree of enhancement also increased with vibration frequency. No broken tip of vibrated micro-needle was found after application. The vibrating solid micro-needle was effective and safe for the transdermal administration of hydrophilic drugs. The effectiveness increases with increasing vibration frequency.
Keywords: Drug delivery; Micro-needle; Permeability; Vibration.