My Research Interests
Transdermal Drug Delivery (TDD) is an area of pharmaceutics that has
experienced a lot of growth over the last
decade. TDD has many advantages over traditional routes of delivery
, such as the oral route. Unfortunately, not all drugs can be
delivered transdermally due to complex barrier of human skin. In
order to overcome this barrier, the use of permeation enhancers has been
proposed. These enhancers are compounds which permeate into the
upperlayer of the skin (stratum corneum) and facilitate the diffusion of drug
molecules. My research focuses on the search for enhancers that are
efficient and also safe. Also, I formulate topical and transdermal
products that contain permeation enhancers and perform permeabiltiy
testing in vitro.
Skin alternaitves where initially developed for skin grafts for individuals
with either serious burns or venous ulcers. Recently, there has been
increased interest in the use of skin alternatives for in vitro permeability
testing for transdermal and topical products.The use of these models for
permeability tested has been limited because of the biological properties of
skin alternatives. Even though these skin alternatives contain the two
predominant cell types found in human skin (keratinocytes and fibroblasts), the
barrier properties of skin alternatives are typically impaired. When one
compares native human skin to skin alternative there are some very distinct
differences. 1) The size of the stratum corneum (SC) in skin alternatives
is much smaller than SC found in native human skin. 2) The lipid
composition of skin alternatives are different than the composition found in
human skin. In particular the polar ceramides (Fraction 6I and 6II) are
underrepresented. 3) As a consequence, the permeability of skin
alternatives is much higher than native human skin. My lab focuses on
ways to improve the biological functionality of skin alternatives. For
example, I am currently modifying culture conditions with vitamin C
supplementation to improve the lipid composition of the skin alternative and
hopefully this will improve the permeability. CLICK
TO SEE A PICTURE OF THE SKIN ALTERNATIVE THAT I GROW.
Peroxisome proliferator-activated receptors (PPARs) are members of the steroid/thyroid nuclear receptor superfamily. Three types of PPARs are thought to exist: PPAR-a, PPAR-g, and PPAR-d. PPARs are nuclear receptors that when activated stimulate specific genes. They are activated by substances that induce peroxisome proliferation, such as hypolipidemic drugs (fibrates) and long chain fatty acids. They have been recently implicated in causing such diseases as colon cancer, elevated cholesterol, and diabetes and are also thought to play a major role in skin development. The development of skin is a very complex phenomenon. Skin is comprised of two primary layers. The bottom layer of skin is referred to as the dermis. The dermis is responsible for providing insulation, nerve and blood vessels networks, as well to provide mechanical support for the upper layer of the skin, the epidermis. The epidermis is composed of a specific cell type called keratinocytes. During the process of skin development the keratinocytes undergo differentiation. Differentiation is the process of changing cellular morphology and biochemical function. The differentiation of epidermal keratinocytes is accompanied by the synthesis of specific lipids, composed mainly of sphingolipids, free fatty acids, cholesterol, and cholesterol sulfate. The PPARS are though to affect skin development by turning on keratinocyte differentiation. Currently it is not known which of the PPARs are important for this phenomenon. I am trying to determine what role PPAR activators have in skin development. I am looking specifically at how PPAR activators afftect histology of human skin. If they can speed up the developement of skin grown in tissue culture and if these activators can be used to modify the lipid composition.