The Use of Fractionated Ablative Lasers as a Transdermal Microporation Technique

Fractionated lasers have acceptable aesthetic outcomes with reduced side effects for the patient. This technology could be applied for other uses such as laser assisted transdermal delivery (TDD). This technology has been demonstrated as feasible in an in vitro setting. The purpose of this thesis was to investigate if this could be translated from the laboratory bench into clinical practice. The histopathological mechanism generated by fractional lasers for facilitating TDD was elucidated with a series of in vivo studies utilizing a porcine animal model. Abdominal skin of a pig was subject to different laser settings and biopsy samples taken for histological analysis. The histopathological pattern generated by the laser was analyzed to determine optimum laser settings. The same animal model was then used to demonstrate systemic absorption of a topically applied study drug (lidocaine). The effect of laser setting in relation to drug absorption was examined by serum blood sampling. In addition, adipocyte derived stem cells were delivered to the dermis. Subsequently a human clinical model was used to prove that laser assisted TDD can be clinically applicable. Patients were subjected to a facial rejuvenation laser procedure prior to application of the study drug and serial blood serum levels were taken. Laser type and influence on systemic absorption of the topically applied study drug (lidocaine) was then investigated. Histopathologically fractionated lasers partially ablated the stratum corneum, and perforated the underlying epidermis/dermis creating ‘microchannels’ which allowed absorption of lidocaine and stem cells. The depth and thermal injury of these microchannels could be determined by changing the laser settings. Enhanced systemic absorption of a topically applied study drug was successfully demonstrated in both animal and human clinical models. The amount of drug absorbed could be manipulated by altering laser settings, but also influenced by factors such as intrinsic enzymatic rate.