Stratum corneum development

STRATUM CORNEUM DEVELOPMENT, MICROSTRUCTURE, AND BARRIER FUNCTION... 

Sweating, the other powerful heat loss mechanism actively regulated by the thermoregulatory center, is most developed in humans. With about 2,6 million sweat glands distributed over the skin and neurally controlled, sweat secretion can vary from 0 to 1 I7(h m ). The other, lesser, passive evaporative process of the skin is from the diffusion of water. The primary resistance to this flow is the stratum corneum or outermost 15 pm of the skin. The diffusion resistance of the skin is high in comparison to that of clothing and the boundary layer resistance and as a result makes water loss by diffusion fairly stable at about 500 grams/day. 

Transdermal Administration. The development of the stratum corneum is complete at birth and is considered to have permeability similar to that of adults, except in preterm infants [81], Preterm neonates and infants have an underdeveloped epidermal barrier and are subject to excessive absorption of potentially toxic ingredients from topically applied products. 

In 2003, Mitragotri developed a model for predicting stratum corneum permeability which included four different pathways. The overall skin permeability was described by the following equation ... 

The major limitation to developing therapeutic proteins in nonparenteral dosage forms is the poor permeability of these water-soluble and hygroscopic macromolecules across the tissue layers at the site of drug administration. These tissue layers include the epithelium of the gastrointestinal tract, the stratum corneum of the skin, and the epithelium lining of the alveoli and nasal cavity. 

To further increase our insight into the stratum corneum barrier function, stratum corneum lipid models have been developed. The main advantage of these lipid models is that the... 

Powder injection applies many of the principles of pulmonary delivery of dry powders to the lungs The drug has to be in the form of very small particles, is dispensed from a reservoir, and is delivered as an aerosol i.e., particles are dispersed in a gas. Liquid or dissolved drug can be delivered by precipitation or adsorption onto carrier particles. The big difference with pulmonary delivery is the momentum at which the particles are delivered. Driven by a high-pressure helium gas stream, the particles travel fast enough to penetrate the outer layer of the skin, the stratum corneum. The design of devices to deliver needle-free injection of solids was pioneered by researchers at the University of Oxford who founded PowderJect Pharmaceuticals PLC in 1993 (now PowderMed Ltd.) to develop the only powder-based technology so far. Since that... 

Propylene glycol is also an effective humectant and increases the water content of the stratum corneum. The hygroscopic characteristics of the agent may help it to develop an osmotic gradient through the stratum corneum, thereby increasing hydration of the outermost layers by drawing water out from the inner layers of the skin. 

Although the stratum corneum acts as a simple physical barrier to outside influences, skin tissue as a whole is very active. It is crucial in maintaining the body s homeostasis, its essential steady-state environment. Skin maintains temperature and balance of electrolytes, the dissolved salts in internal body fluids. It is metabolically active and participates in hormonal and immune regulatory processes. More than serving as a passive barrier, it is proactive in response to xenobiotic insults and can be damaged in the defensive process by developing rashes and other symptoms. 

The evolution of life in the relatively dry terrestrial environment required the development of a waterproof integument.1 In the terrestrial vertebrates, the stratum corneum provides the primary barrier to water loss. The barrier function of the stratum corneum depends upon a unique mixture of lipids that form lamellar structures in the intercellular spaces.2-5 This generally consists of ceramides, cholesterol, and long chain fatty acids. 

The physical state and molecular organization of the stratum corneum intercellular lipid matrix largely determines the hydration-level of the stratum corneum and thus, indirectly, the mechanical properties and appearance of the skin. A better understanding of stratum corneum lipid organization may thus aid the development of more efficient cosmetic formulations. 

Scott, I.R. and Harding, C.R., Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment, Dev. Biol., 115, 84—92, 1986. 

Behne, M.J. et al., Neonatal development of the stratum corneum pH gradient localization and mechanisms leading to emergence of optimal barrier function, J. Invest. Dermatol., 120, 998, 2003. 

The importance of water to the proper functioning of the Stratum Corneum (SC) is well-recognized. The reliable quantification of water in the corneum and its interaction with topically applied products is, in fact, essential for understanding skin physiology and developing efficient skin care formulation. 

Lipid Extracts. Lipids were extracted from the hairless mouse stratum corneum using a modified method based on methods developed by Bligh and Dyer (37) and Elias and coworkers (17.20.21). 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

Due to the brick-and-mortar structure of the stratum corneum, the skin is a difficult layer to permeate across for most active pharmaceutical ingredients. Because of this diffusional barrier, new strategies have been developed to allow compounds to better penetrate the stratum corneum [28], These strategies can be defined as either chemical or physical approaches to disrupting the barrier function of the skin. 

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