Combined Laser and Medicated Scar Improvement Therapies, 01-R8276
Principal Investigators
Gianny J. Rossini
Gloria E. Gutierrez
Lucy M. Kimmel
Alda E. Flores
Inclusive Dates: 01/01/12 – 01/01/13
Background — Ablative CO2 laser resurfacing of the entire skin surface has been the FDA-approved standard of care for cosmetic enhancement and scar improvement, albeit with considerable risk of infection and loss of efficacy for deep burn scars and for wounds of large area extent. This procedure creates a tissue column or skin poration of about 2-mm deep and 300-µm wide named microablative zone (MAZ) using the focal thermal power of a CO2 laser. After a short period of time, the MAZ is replaced by cell migration from the adjacent healthy tissue. However, this method appears to be useful only for relatively shallow scars not penetrating into the dermis. Therefore, to improve the laser procedure, drug enhancers, such as corticosteroids and similar derivatives, are commonly used as injections or creams; however, corticosteroids are quite hydrophobic and form a suspension containing crystals of wide size distribution (greater than 10 µm). It is unclear how effectively they can penetrate the skin through the MAZ. Clearly, specially designed formulations with improved permeability and controlled-release characteristics and delayed controlled-release of commonly used corticosteroids such as triamcinolone acetonide are needed. These formulations may not present known side effects such as skin atrophy and associated infections and might be able to enhance the anti-scarring effects providing physicians with additional options when treating large scars, in particular the ones seen after burns.
Approach — The project team developed advanced dermal drug delivery formulations known as flexible liposomes, cubosomes, ethosomes, and transferosomes; each of these technologies offers nonoverlapping benefits. For example, cubosomes use waxy lipids and starch and are good for loading hard to dissolve drugs. Ethosomes are made with flexible lipids and a high content (20 to 30 percent) of ethanol to make them highly efficient in penetrating the stratum corneum of the skin. Transferosomes are made with flexible lipids and surfactants to increase surface fluidity and to permeate the stratum corneum of the skin. For these basic formulations, the use of additives such as natural-derived detergents and others were investigated in order to improve dermal permeation, while at the same time avoiding the use of cholesterol or other rigid chemical structural components. Carbopol was also included as a thickening agent to allow for easier application to the skin. As a standard procedure, nanoparticle size was measured using photon correlation spectroscopy (PCS) particle analyzer and surface charge using a ZetaPal analyzer. Formulation flexibility index is measured by extrusion across a nanoporous membrane under constant pressure; permeability testing is assessed with a Franz cell device using skin from cadavers obtained under Institutional Review Board (IRB) regulations or using synthetic membranes that mimic skin permeability. Efficacy of dermal formulations is determined in vivo in a rabbit ear scar model, a well-established model for testing scar medication. In addition, this standard model will be investigated to also test laser therapies, a valuable tool for research of new dermal formulations for scar improvement.
Accomplishments — Flexible dermal formulations known as cubosomes, ethosomes, and transferosomes loaded with corticosteroids were fabricated and characterized for drug loading, drug release, particle size, and drug permeability using human cadaver skin and artificial skin substitutes. A pilot study with a small number of rabbits is in progress; this study will establish the model and allow for future testing of lead formulations in vivo with and without ablative laser procedures.
