Design and Assessment of a Laser-Assisted Intradermal Medication: A Prospective Randomised Case-control Clinical Trial

Human skin is a potential route for drug administration. Although some inherent cutaneous pathways assist in transporting drugs into the skin, so effective is the stratum corneum that most of the drugs applied do not exhibit the necessary lipophilicity or are too large to permeate this barrier in a significant concentration. Research aimed at optimising device-assisted transcutaneous medication is a novel paradigm and essential to expanding the drugs suitable for application via the skin. The importance of this research is emphasised by the gap in the literature concerning the use of fractional ablative lasers as physical penetration enhancers to bypass the barrier to drug penetration offered by the stratum corneum, allowing for a significant increase in dermal bioavailability of many pharmaceutical agents. The literature has suggested that drugs can diffuse into the microchannels produced by the lasers and penetrate directly to the dermis but usually do not investigate comparative studies on clinical outcomes. Convincing data has been restricted to the oncology field, and larger, controlled trials are necessary to evaluate the impact on the skin surface and the quantitative and qualitative effectiveness of the method. Despite the promising results, the lack of standard methodology regarding laser protocols and for analysing the results reinforces the need for comprehensive research to establish laser-assisted medication as a standard therapeutic modality. This is the first study that has validated and employed three-dimensional stereophotogrammetry as a tool to provide accurate quantification of the skin’s microtopography before and after laser-assisted medication. The stereophotogrammetry system provided accurate numerical data corresponding to the influence of laser-assisted medication on the surface of wrinkles and scars. The thesis original contribution to knowledge included the design of a reproducible, active, laser-assisted, intradermal delivery of medication. An in vivo, prospective, randomised, double-blind, comparative clinical trial was designed. Consenting patients presenting wrinkles and scars were randomised and subjected to one session of laser skin resurfacing with a 2,940 nm Er:YAG (Erbium dopped Yttrium Aluminium Garnet) fractional ablative laser followed by immediate topical application of the medication. The laser parameters were standardised for all patients. This is the first robust study that has compared the effect of different substances on the skin surface after laser-resurfacing and on different conditions of skin integrity, scars and wrinkles. A control group received vitamin C immediately after laser skin resurfacing and another study group received vitamin C plus a cosmeceutical containing growth factors. Most patients treated presented an improvement in the skin condition. However, the groups receiving the cosmeceutical containing growth factors exhibited statistically significantly better results compared to the control groups receiving vitamin C only. This finding demonstrates the positive effect of laser-assisted medication on skin surface and that the addition of growth factors to formulae enhances the result of the treatment.