Permeability of pig urinary bladder wall: Time and concentration dependent effect of chitosan
Permeability of pig urinary bladder wall: Time and concentration dependent effect of chitosan
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DOI：
10.1248/bpb.29.1685
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发表时间：
2006-08-01
影响因子：
2
通讯作者：
Mrhar, Ales
中科院分区：
文献类型：
--
作者：
Kos, Mojca Kerec;Bogataj, Marija;Mrhar, Ales
我们先前的研究证实，0.5%w/v浓度的壳聚糖可通过尿路上皮剥离来增加猪膀胱壁的通透性。本工作的目的是确定壳聚糖对模型药物渗透到膀胱壁的作用的时间和浓度依赖关系，并确定促进渗透的机制是否依赖于所用壳聚糖的浓度。在用扩散池进行的渗透性研究中，测定了模型药物莫西沙星在猪膀胱壁中的转运。为了观察尿路上皮对壳聚糖处理的反应，使用了扫描和透射电子显微镜。在90min内，壳聚糖对莫西沙星组织量的影响逐渐增加，并接近平台期。在1h内，即使是0.0005%w/v的壳聚糖分散体也能显着提高猪膀胱壁对模型药物的通透性，且在0.001%w/v浓度时对组织通透性的影响最大。显著增加膀胱壁通透性的所有浓度的壳聚糖都会导致表面细胞坏死或尿路上皮脱屑。然而，在较低浓度和较短暴露时间下，对尿路上皮的损伤仅限于紧密连接的变化。确定壳聚糖以时间和浓度依赖的方式增加莫西沙星在膀胱壁的渗透。
Chitosan in 0.5% w/v concentration enhanced the permeability of the isolated pig urinary bladder wall by desquamation of the urothelium as ascertained in our previous study. The aim of the present work was to determine the time and concentration dependence of chitosan's effect on the permeation of a model drug into the bladder wall and to establish if the mechanism of permeation enhancement depends on the concentration of chitosan used. In the permeability studies performed by the use of diffusion cells, transport of a model drug moxifloxacin into the isolated pig urinary bladder wall was determined. For morphological observations of the urothelium in response to chitosan treatment scanning and transmission electron microscopy were applied. Within 90 min the effect of chitosan on the tissue amounts of moxifloxacin gradually increased and approached its plateau. In one hour even 0.0005% w/v dispersion of chitosan significantly enhanced the permeability of the pig urinary bladder wall for the model drug and at 0.001% w/v concentration the maximal effect on the tissue permeability was achieved. All concentrations of chitosan that significantly enhanced the permeability of the bladder wall triggered necrosis of superficial cells or desquamation of the urothelium. However, at lower concentrations and shorter exposure times the damage of the urothelium was limited to the changes in tight junctions. Chitosan was ascertained to increase the permeation of moxifloxacin into the urinary bladder wall in a time and concentration dependent manner.