Triptolide (TP), a major active component of Triptelygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase th...Triptolide (TP), a major active component of Triptelygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP), has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA). The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one compartment open model. The relationship equation between plasma concentration and time was C=303.59 x (e(-0.064t)-e(-0.287t)). The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1a in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1/3 and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Thl and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
3D-Honeycombed CL-20 structures with low critical size of detonation have been fabricated successfully for intelligent weapon systems using a micro-flow direct ink writing(DIW) technology.The CL-20-based explosive ink...3D-Honeycombed CL-20 structures with low critical size of detonation have been fabricated successfully for intelligent weapon systems using a micro-flow direct ink writing(DIW) technology.The CL-20-based explosive ink for DIW technology was prepared by a two-component adhesive system with waterborne polyurethane(WPU) and ethyl cellulose(EC).Not only the preparation of the explosive ink but also the principle of DIW process have been investigated systematically.The explosive ink displayed stro ng shea rthinning behavior that permitted layer-by-laye r deposition from a fine nozzle onto a substrate to produce complex shapes.The EC content was varied to alter the pore structure distribution and rheological behavior of ink samples after curing.The deposited explosive composite materials are of a honeycombed structure with high porosity,and the pore size distribution increases with the increase of EC content.No phase change was observed during the preparation process.Both WPU and EC show good compatibility with CL-20 particles.Apparently high activation energy was realized in the CL-20-based composite ink compared with that of the refined CL-20 due to the presence of non-energetic but stable WPU.The detonation performance of the composite materials can be precisely controlled by an adjustment in the content of binders.The 3D honeyco mbed CL-20 structures,which are fabricated by DIW technology,have a very small critical detonation size of less than 69 μm,as demonstrated by wedge shaped charge test.The ink can be used to create 3D structures with complex geometries not possible with traditional manufacturing techniques,which presents a bright future for the development of intelligent weapon systems.展开更多
基金supported by National Science and Technology Major Project on Significant Creation of New Drugs of China(2009ZX09502-019)
文摘Triptolide (TP), a major active component of Triptelygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP), has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA). The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one compartment open model. The relationship equation between plasma concentration and time was C=303.59 x (e(-0.064t)-e(-0.287t)). The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1a in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1/3 and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Thl and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
基金This research work was financially supported by the Advantage Disciplines Climbing Plan of Shanxi Province and Graduate Education Innovation Project in Shanxi Province(2016BY119).
文摘3D-Honeycombed CL-20 structures with low critical size of detonation have been fabricated successfully for intelligent weapon systems using a micro-flow direct ink writing(DIW) technology.The CL-20-based explosive ink for DIW technology was prepared by a two-component adhesive system with waterborne polyurethane(WPU) and ethyl cellulose(EC).Not only the preparation of the explosive ink but also the principle of DIW process have been investigated systematically.The explosive ink displayed stro ng shea rthinning behavior that permitted layer-by-laye r deposition from a fine nozzle onto a substrate to produce complex shapes.The EC content was varied to alter the pore structure distribution and rheological behavior of ink samples after curing.The deposited explosive composite materials are of a honeycombed structure with high porosity,and the pore size distribution increases with the increase of EC content.No phase change was observed during the preparation process.Both WPU and EC show good compatibility with CL-20 particles.Apparently high activation energy was realized in the CL-20-based composite ink compared with that of the refined CL-20 due to the presence of non-energetic but stable WPU.The detonation performance of the composite materials can be precisely controlled by an adjustment in the content of binders.The 3D honeyco mbed CL-20 structures,which are fabricated by DIW technology,have a very small critical detonation size of less than 69 μm,as demonstrated by wedge shaped charge test.The ink can be used to create 3D structures with complex geometries not possible with traditional manufacturing techniques,which presents a bright future for the development of intelligent weapon systems.
