| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Micro- and nano-particles have been used for efficient delivery of drugs and diagnostic agents to lymphatic system. Interstitially administered particles are known to be taken up into initial lymphatics and accumulate in the regional lymph nodes. Little information, however, exists regarding size-dependent mechanisms for the particle uptake and accumulation in the lymph nodes in vivo. Thus, in this study, we have attempted to evaluate effects of size on uptake and accumulation of colloidal particles in the lymph nodes. Male Japan White rabbits were anesthetized with ketamine (20 mg/kg iv.) and pentobarbital (20 mg/kg iv.). Retrograde cannulation was performed in one of the popliteal afferent lymph vessels. Labeled latex with fluorescence microspheres with 0.5, 1.1, 2.0, 5.6 and 10.0 μm in diameter were injected subcutaneously at dorsal portion of rabbit foot. Then, concentrations of the microspheres in the efferent lymph vessel were determined by measuring the number of the particles u
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nder a fluorescent microscope. In other experiments, centripetal and retrograde cannulations were performed in one of the popliteal afferent and efferent lymph vessels, respectively. All other efferent lymphatics were ligated completely. Labeled latex with fluorescence microspheres with 0.5, 1.1, 1.7 and 1.9 μm in diameter were injected into the afferent lymph vessel. Two microgram of each particle was administered at one time and artificial lymph fluid was injected through the same route at constant rate of 1.47 ml/h. Then, changes in concentration of the microspheres in the efferent lymph vessel were determined by measuring the number of the particles under a fluorescent microscope. The decreasing order of particle concentration in afferent lymph was as follows : 0.5μm> 1.1μm >2.0 μm-particle. No particle with 5.6 and 10.0 μm in diameter was observed in the afferent lymph. When mechanical massage was administered on the injection site, both lymph flow rate and particle concentration were markedly increased. In the latter experiments, 11.0 ±6.4% of the 0.5 μm-microsphere passed through the lymph node in 2.5h. On the other hand, no microsphere with 1.9μm in diameter was observed in the efferent lymph. The decreasing order of ability for accumulating in the lymph node was as follows : 1.9μm>1.7μm>1.1μm>0.5μm-microsphere. These results strongly suggest that size- and mechanical stimulation-dependent mechanisms exist in transport of micro- and nano-particles from subcutaneous tissue into the lymphatic system and that size-dependent accumulating mechanisms exist in the lymph node. Less
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