Despite the existence of several depigmenting agents, the treatment of melasma is long and complicated, mainly because it is difficult for these substances to penetrate the skin.
Indeed, the stratum corneum (SC), the outermost layer of the skin, is the main obstacle to the drugs’ percutaneous absorption because its barrier function significantly restricts the drugs’ transdermal delivery.
It ranges from 10 to 20 μm in thickness and consists of highly differentiated keratinocytes (corneocytes) embedded in an intercellular lipid matrix of mainly fatty acids, ceramides, cholesterol, and cholesterol sulfate. To penetrate into the skin, drug molecules must be small in size and/or low molecular weight. Lipophilic molecules can penetrate the skin deeper than hydrophilic ones. In the last few years, the transdermal delivery of active substances has become an important therapy used in treating a large number of skin diseases.
Skin penetration enhancement can be achieved either physically or chemically. Many techniques have been developed to improve transdermal drug delivery, such as electroporation, sonophoresis, and iontophoresis, which are able to improve the stratum corneum layer permeability and to enhance penetration of topical agents through the skin.
Recently, the use of skin needling has been proposed as a new physical strategy to increase transdermal drug delivery. Since, 1995 this technique has been used to achieve percutaneous collagen induction in order to reduce skin imperfections]. To date, skin needling has mostly been proposed as an effective method of treating scars and wrinkles, and it is carried out by rolling a special device over the skin comprising a rolling barrel fitted with a variable number of microneedles. The micro-needles penetrate through the epidermis but do not remove it; the epidermis is only punctured and heals rapidly. The needles seem to separate the cells from one another rather than cut through them, and thus many cells are spared. Because the needles are set in a roller, every needle initially penetrates at an angle and then goes deeper as the roller turns. Finally, the needle is extracted at a converse angle, therefore curving the tracts and reflecting the path of the needle as it rolls into and then out of the skin for about 0.5 mm into the dermis. The epidermis, and particularly the stratum corneum, remains intact except for the minute holes, which are about four cells in diameter. In 1998, Henry et al., in the first study on microneedle use for transdermal drug delivery, showed an increase in magnitude of four levels in the permeability of human skin after the insertion of an array of 150 μm long, solid silicon, out-of-plane microneedles. More recently, several authors have shown that microneedle-injected sites have a significantly higher transdermal penetration. Recent reports have tried to identify the mechanisms involved in the enhancement of transdermal drug delivery and several hypotheses have been proposed, though none is completely exhaustive.
To understand the mechanism by which microneedles increase skin permeability, McAllister et al. theoretically modelled transdermal transport as diffusion through holes of known geometry made by insertion of microneedles. All the scientific data is based on a repetitive rolling (10 to 15 times) on the same area of the skin. In this case around 240 microinfiltration pores per square centimeter are set and all of these pores close within minutes.
It may be that the microneedles aid in bypassing the stratum corneum and enhancing drug delivery through the skin by increasing skin blood perfusion also. A Laser Doppler Perfusion Monitor was used to record maximum blood flow and the time needed to reach maximum blood flow in the treatment areas. Sections treated with microneedles showed a higher maximum blood flow and reached maximum blood flow faster than sites not treated with microneedles.
Conclusions of the Study
This pilot study describes the first report of improvement in melasma through the use of skin needling in combination with a depigmenting serum, and shows that combination therapy with skin needling and topical depigmenting serum is more effective than topical depigmenting serum alone in improving melasma. As this was a pilot study, we have neither a large sample size nor a long-term followup; a larger sample and longer followups are needed to assess the long-term efficacy of our results. Potential refinement of the number of sessions and treatment parameters call for further evaluation in order to maximize the therapeutic efficacy of this new way of treating melasma, but it opens new perspectives for employment of this device to enhance the penetration of depigmenting compounds and to reduce treatment times.
G. Fabbrocini, V. De Vita, N. Fardella, F. Pastore, M. C. Annunziata, M. C. Mauriello, A. Monfrecola, and N. Cameli
Section of Dermatology, Department of Systematic Pathology, University of Naples Federico, Street Sergio Pansini 5, 80133 Napoli, Italy
2San Gallicano Dermatological Institute, Street Elio Chianesi 53, 00144 Rome, Italy.
Academic Editor: Bishara S. Atiyeh