| Recent advances in biotechnology have resulted in a significant increase in the number of therapeutic macromolecules that are reaching the clinical application. Although earlier development was restricted to recombinant DNA and monoclonal antibodies, the field of biotechnology has rapidly expanded into other areas, such as peptides, proteins, carbohydrates, oligonucleotides and other gene-based compounds. Clinical application of these bioactive macromolecules has been limited by "the first pass" in the liver or degradation of enzymes in the gastrointestinal tract for oral use as well as difficult maintenance in blood concentration of the drug for injection. Transdermal drug delivery (TDD) is an alternative method of drug delivery that draws attention as a potential administration of biological pharmacy.Patching the drug on the skin, the drug molecules permeate through the skin into the subcutaneous capillary vessels by passive, physics and chemical enhancing diffusion. However, very few drugs can be administered transdermally at therapeutic levels to the barrier of stratum corneum (SC), the skin's outer layer.Several physical and chemical methods, including iontophoresis, electroporation, sonophoresis, photomechanical wave, magnetophoresis and chemical enhancers, are applied to improve the permeability of skin. In the system of TDD, mass transport is an irreversible and non-equilibrium thermodynamical process whose penetration is in great relation to outside force field, skin speciality, physical and chemical properties of drug, and so on.Five achievements have be obtained in the research of biophysical phenomena for drug pass through SC, including below:1. Phenomenological analysis of mass transport through Stratum Corneum. Supposing the system of side-by-side permeation chambers constant emperature, no chemical reaction, non-viscosity solution, two species and local equilibrium, establish dissipation function for the system on the basis of Gibbs function to determine mass flow and volume flow, as well as volume force and surface force. Tinidazole as pattern substance, the experiment was carried out by three groups of control test (passive diffusion) and experiment test (electric pulse diffusion), pulse protocol including: pulse voltage l/o=94-400V, pulse rate R =1-4 ppm, pulse number N = 50, storage capacitor C = 4.7, 22, 47, 100 nF. Results include (1) not only substance transdermal permeation, but volume loss of solution occurrs in the system; (2) according to experimental data, phenomenological coefficient is time variable, the action of surface force on mass flow and volume force on volume flow decreases as time decays; (3) volume flow may came into being by velocity grads arising from solution convection on the surface of stratum corneum (SC). Ity is determinated the system of drug permeation through SC in side-by-side permeation chambers is a non-linear and time-variable system.2. Non-Equilibrium Properties of Drug Permeation through SC in Vitro. The system of side-by-side permeation chambers in vitro was supposed to be isolated, thus conditions for equilibrium state were decided. And a network thermodynamic model was established. We completed non-equilibrium and leakage experiments with which Tinidazole was pattern drug. The properties of non-equilibrium including: (1) Long term to reach equilibrium state; (2) Delay-start of the permeation; and (3) Uncertainty of initial drug permeable flux. The properties of leakage including: (1) Degression of drug permeable flux; and (2) Changeability of permeation time constant.3. Changes of electrical and flux properties of SC caused by high-voltage pulse. To suggest an analogous membrane model for SC including conductance of appendageal, lipid, lipid-corneocyte matrix pathway and Nernst potential of charged drug molecule. Leakage experiments with Tinidazole as pattern masswere carried out with three groups each of which contained 15 protocols that electrodes applied high-voltage puls...
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