Fish skin as a model membrane: structure and characteristics.

OBJECTIVES: Synthetic and cell-based membranes are frequently used during drug formulation development for the assessment of drug availability. However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane. METHOD: Permeation of hydrocortisone, lidocaine hydrochloride, benzocaine, diethylstilbestrol, naproxen, picric acid and sodium nitrate through skin from a freshly caught catfish was determined in Franz diffusion cells. KEY FINDINGS: Both lipophilic and hydrophilic molecules permeate through catfish skin via hydrated channels or aqueous pores. No correlation was observed between the octanol/water partition coefficient of the permeating molecules and their permeability coefficient through the skin. Permeation through catfish skin was found to be diffusion controlled. CONCLUSIONS: The results suggest that permeation through the fish skin proceeds via a diffusion-controlled process, a process that is similar to drug permeation through the aqueous mucous layer of a mucosal membrane. In addition, the fish skin, with its collagen matrix structure, appears to possess similar properties to the eye sclera.

Effects of cyclodextrins on drug delivery through biological membranes.

Cyclodextrins have proven themselves to be useful functional excipients. Cyclodextrin derivatives can be hydrophilic or relatively lipophilic based on their substitution and these properties can give insight into their ability to act as permeability enhancers. Lipophilic cyclodextrins such as the methylated derivatives are thought to increase drug flux by altering barrier properties of the membrane through component extraction or fluidization. The hydrophilic cyclodextrin family also modulate drug flux through membranes but via different mechanisms. The current effort seeks to provide various explanations for these observations based on interactions of hydrophilic cyclodextrins with the unstirred water layer that separates the bulk media from biological membranes such as the gastric mucosa, cornea and reproductive tract. Theories on the serial nature of resistances to drug flux are used to explain why hydrophilic cyclodextrins can enhance drug uptake in some situation (i.e., for lipophilic material) but not in others. In addition, the nature of secondary equilibria and competition between cyclodextrins and rheologically important biopolymers such as mucin are assessed to give a complete picture of the effect of these starch derivatives. This information can be useful not only in understanding the actions of cyclodextrin but also in expanding their application and uses.

Development and evaluation of an artificial membrane for determination of drug availability.

Various artificial membranes (e.g. PAMPA) and cellular-based membranes (e.g. Caco-2) are used for screening during early stages of drug discovery. However, these methods are not well suited for evaluation of pharmaceutical formulations and the effects of various excipients on drug availability. When drug molecules permeate biological membranes they encounter two types of permeation resistance, a membrane resistance in the lipophilic membrane and diffusion resistance in the unstirred water layers adjacent to both surfaces of the lipophilic membrane. We have developed an artificial membrane that is cheap and simple to prepare. The unstirred water layer consists of a hydrated semi-permeable cellophane membrane with a molecular weight cutoff (MWCO) of 12,000-14,000 Da and a lipophilic membrane of pure n-octanol in a nitrocellulose matrix. In the diffusion cell the hydrated cellophane membrane (thickness 210-230 microm) is on the donor side and the lipophilic octanol membrane (thickness about 120 microm) on the receptor side. Permeation of ionizable lipophilic drug molecules was diffusion-controlled when the drug was unionized but lipophilic membrane controlled when the drug was ionized. Drug permeation patterns from cyclodextrin containing formulations through the membrane were similar to those previously observed for biological membranes such as hairless mouse skin and the eye cornea.

Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study.

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care.