Macromolecule Transport Through Epidermis By Electroporation

Recent advances in biotechnology have resulted in a significant increase in the number of therapeutic macromolecules that are reaching the clinical application. 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. So people pay more attention to study new novel delivery system and transdermal drug delivery (TDD) is proposed under the background. TDD is that patching the drug on the skin, the drug molecules permeate through the skin into the subcutaneous capillary vessels. 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, photomechanical wave, sonophoresis, magnetophoresis and chemical enhancers, are applied to improve the permeability of skin. In this paper we use electroporation as assistant technology.In one word, it is essential to study the theory of drug delivery system and it is also a important project to find a appropriate, safe and effective system. In this thesis we use fluorescein isothiocyanate-dextran FD-4 and FD-20s as model macromolecule to study factors that affecttransdermal drug delivery by electropration. And also we study the phenomenological equation and describe the change of skin resistance. So we draw a conclusion that electroporation can effectively increase the transport of macromolecule through skin and it is potential to transport insulin.Three achievements have be obtained in the research of biophysical phenomena for macromolecule pass through epidermis, including below:1. The factors of affect substance transporting through skin in electrical pulse. Using FD-4 and FD-20s as model substance. Experiment date indicate that electroporation can effectively enhance transport of FD-4 and FD-20s, and also find that voltage, capacitance, molecular weight and different part affect the substance transport. Molecular weight of FD-20s is 19500 Da and is more than molecular weight of insulin whose is 5800 Da, so we propose that molecular weight is not mostly reason to affect substance transport, and then it is a potential to transport insulin through skin by electroporation.2. Resistance of skin in electrical pulse: Results show; (1) We obtained that resistance of across epidermis decreased along with initial voltage of pulse increased using logarithm trend line fitting; (2) in same pulse duty voltage decreased with time expand but resistance of across SC increased.3. 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. FD-4 and FD-20s 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 Vo=l00-400V, pulse rate R =lppm, pulse number N = 30, storage capacitor C - 22, 47, l00F. Results include (I) not only substance transdermal permeation, but volume loss of solution occurrs in the system; (2) according to experimental data, phenomenological coefficient is not time variable, and volume can increase as energy expand; (3) different substance property can affect solution volume and can get different results.