Characterization of human sclera barrier properties for transscleral delivery of bevacizumab and ranibizumab.
Characterization of human sclera barrier properties for transscleral delivery of bevacizumab and ranibizumab.
复制标题
DOI：
10.1002/jps.23387
复制
发表时间：
2013-03
影响因子：
3.8
通讯作者：
Li, S. Kevin
中科院分区：
文献类型：
--
作者：
Wen, He;Hao, Jinsong;Li, S. Kevin
关键词：
本研究的目的是（a）研究抗血管内皮生长因子药物贝伐单抗和雷珠单抗的经巩膜渗透性，以及（b）使用贝伐单抗、雷珠单抗、异硫氰酸荧光素（FITC）标记的牛血清白蛋白（FITC-BSA）、FITC 标记的聚蔗糖检查大分子的分子结构对穿过人体巩膜渗透的影响(FITC-ficoll) 和 FITC 标记的葡聚糖 (FITC-dextrans) 体外试验。使用动态光散射测量大分子的流体动力学半径，在摄取实验中确定它们对巩膜的分配系数，并在并排扩散池的传输实验中评估它们的渗透系数和穿过巩膜的传输滞后时间。大分子对巩膜的分配系数相对较低。发现 FITC-BSA 的分配系数与其在平衡溶液中的浓度相关，而对于其他大分子，没有观察到特定的浓度依赖性。由于其分子尺寸和扩散受阻，大分子表现出相对较低的渗透系数和较长的传输滞后时间。贝伐单抗、雷珠单抗和 FITC-BSA 比分子量相当的 FITC-葡聚糖和 FITC-ficoll 表现出更低的经巩膜渗透性和更长的转运滞后时间，这可能是因为多糖的柔性结构。因此，多糖可能不是在经巩膜递送研究中模拟治疗性蛋白质经巩膜转运的良好替代渗透剂。
The objectives of this study were to (a) investigate transscleral permeation of antivascular endothelial growth factor drugs bevacizumab and ranibizumab and (b) examine the effects of molecular structures of macromolecules upon permeation across human sclera using bevacizumab, ranibizumab, fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA), FITC-labeled ficoll (FITC-ficoll), and FITC-labeled dextrans (FITC-dextrans) in vitro. The hydrodynamic radii of the macromolecules were measured using dynamic light scattering, their partition coefficients to sclera were determined in uptake experiments, and their permeability coefficients and transport lag times across sclera were evaluated in transport experiments of side-by-side diffusion cells. Macromolecules showed relatively low partition coefficients to sclera. The partition coefficient of FITC-BSA was found to be related to its concentration in the equilibration solution, whereas for other macromolecules, no specific concentration dependency was observed. The macromolecules displayed relatively low permeability coefficients and long transport lag times because of their molecular sizes and hindered diffusion. Bevacizumab, ranibizumab, and FITC-BSA exhibited lower transscleral permeability and longer transport lag times than FITC-dextrans and FITC-ficoll of comparable molecular weights possibly because of the flexible structures of the polysaccharides. Thus, the polysaccharides may not be good surrogate permeants to model transscleral transport of therapeutic proteins in transscleral delivery studies.
登录
查看更多内容
影响因子：
5.8
作者：
Chopra, Poonam;Hao, Jinsong;Li, S. Kevin
通讯作者：
Li, S. Kevin
影响因子：
2.8
作者：
Boehme, Ute;Scheler, Ulrich
通讯作者：
Scheler, Ulrich
影响因子：
6.3
作者：
Asgeirsson, D.;Venturoli, D.;Rippe, C.
通讯作者：
Rippe, C.
影响因子：
3.3
作者：
Pescina, Silvia;Ferrari, Giulio;Nicoli, Sara
通讯作者：
Nicoli, Sara
DOI：
10.2147/opth.s12846
发表时间：
2010-11-10
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Frenkel RE;Haji SA;La M;Frenkel MP;Reyes A
通讯作者：
Reyes A