The mechanism of drug penetration is associated with the complex morphological structure of epithelial tissues and physical and chemical features of the penetrating substance itself. Different layers of epithelial tissues have different resistance to the penetrating substance from the external environment in the body.
The epithelial barrier, the functions of which are to protect against the penetration of pathogenic bacteria and viruses, various antigens and non-invasive substances into the body, is divided into a caring flat multi-layer epithelium – epidermis of the skin (its corneal layer) and non-aridening flat multi-layer epithelium – nasal mucosa, oral cavity, gastrointestinal tract, including the rectum, vagina, cornea of the eye.
Epithelium is covered with water-lipid mantle. Thus, the hydrolipid mantle of the skin is a mixture of sebum (sebum), sweat, residual substances from the process of keratinization (cornification) and skin microflora, and mucus of the mucous layer of the nasal cavity a priory hydrophobic. Epithelial mucus consists of water – 56%, wax ethers – 26% and mucin – 18%. Epidermis lipids consist of 25% triglycerides, 40% ceramides and 35% neutral lipids and free fatty acids.
Fat-soluble substances penetrate the barrier well and can pull other substances with them, such as tocopherol acetate (vit.E). Water and water-soluble substances do not dissolve in fat, so they do not penetrate the barrier.
The penetration of medicinal substances through the epithelial barrier is facilitated by the so-called “transepithelial therapeutic systems” (TETS) – dosed soft dosage forms for external use in the form of paste, ointment, cream, gel, emulsion, solution, powder, suspension, medicinal adhesive film, varnish, etc., which are not dissolved in fat. Physical and chemical properties of TETS allow prescribing drugs with large molecular sizes, such as proteins and other biotechnological products.
Transepithelial delivery of drugs has several advantages: – In comparison with oral prescription, it is possible to ensure faster action of drugs; – it is possible to avoid problems associated with oral administration: inactivation or reduction of drug activity as a result of the first passageway and gastric metabolism; – possibility of immediate termination of treatment at development of adverse reactions; – maintenance of constant concentration of the drug in blood, without fluctuations in concentration; – decrease in frequency of prescription due to delivery of a necessary dose of the drug in a longer period of time; – improvement of patients’ compliance (an easy way of application of the drug); – reduction of a necessary dose of the drug, as losses of the drug connected with its use are reduced.
To date, transepithelial therapeutic systems allow to reliably overcome epithelial barriers of skin and mucous membranes, provide support for constant therapeutic concentration of the substance in tissues and plasma, preventing significant time fluctuations.