RÉSUMÉ
AIM: To illustrate the non-equilibrium properties of drug permeation through stratum corneum (SC) to provide theory and method for transdermal drug delivery. METHODS: The system of side-by-side permeation chambers in vitro was isolated, thus conditions for equilibrium state were decided. And a network thermodynamic model was established. Non-equilibrium and leakage experiments were completed with which tinidazole was pattern drug. RESULTS: The properties of non-equilibrium including: long term to reach equilibrium state; delay-start of the permeation; uncertainty of initial drug permeable flux. The properties of leakage including: degression of drug permeable flux; changeability of permeation time constant. CONCLUSION: The permeation cell is believed to be a non-linear and time variable system.
Sujet(s)
Épiderme/métabolisme , Tinidazole/pharmacocinétique , Administration par voie cutanée , Électroporation , Humains , Techniques in vitro , Perméabilité , Tinidazole/administration et posologieRÉSUMÉ
Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF-R, permitting the recruitment of gp130 and LIF-R, forming a tripartite receptor complex. Cells that only express gp130 and LIF-R, but not CNTF-R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH-terminus of sCNTF-R to the NH2-terminus of CNTF. Recombinant CNTF/sCNTF-R fusion protein (Hyper-CNTF) was successfully expressed in COS-7 cells. The apparent molecular mass of the Hyper-CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper-CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF-R and LIF-R receptor subunit whereas Hyper-CNTF required heterodimerization of the gp130 and LIF-R receptor subunit. We concluded that the fusion protein Hyper-CNTF had superagonistic activity on target cells expressing gp130 and LIF-R, but lacking membrane-bound CNTF-R.