Effect of benzalkonium chloride on transscleral drug delivery
Effect of benzalkonium chloride on transscleral drug delivery
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DOI：
10.1167/iovs.03-0934
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Ogura, Y
中科院分区：
文献类型：
--
作者：
Okabe, K;Kimura, H;Ogura, Y
目的.目的观察苯扎氯铵经巩膜给药的安全性和有效性。用渗透泵连续给白化病兔巩膜注射21-磷酸倍他米松（BP）水溶液（含或不含苯扎氯铵（巴克））1周。通过高效液相色谱法（HPLC）测定房水、玻璃体和视网膜-脉络膜中的BP浓度。为了研究巴克对BP体外巩膜渗透性的影响，使用双腔Ussing装置评价了含有或不含巴克的BP水溶液穿过兔巩膜的渗透性。为了确定巴克对大分子的经巩膜递送的影响，通过渗透泵将20-和70- kDa异硫氰酸荧光素（FITC）-葡聚糖（分别为FD- 20和-70）水溶液（有或没有巴克）连续施用至巩膜。在植入泵后1周，通过荧光分光光度法测量房水、玻璃体和视网膜-脉络膜中的荧光强度。电生理学和组织学评价巴克的视网膜毒性。与对照组相比，巴克增加了玻璃体和视网膜-脉络膜中BP的浓度。在房水中未检测到BP。在体外研究中，巴克不增加BP的巩膜渗透性。在视网膜-脉络膜中，巴克显著增加FD- 20的浓度，但不增加FD- 70的浓度。巴克的加入没有增加玻璃体中FD- 20或-70的浓度。在电生理和组织学检查中，加入BAK后未观察到明显的视网膜毒性反应。本研究的结果表明，巴克可以改善药物在经巩膜给药系统中的眼部渗透而不产生毒性反应。
PURPOSE. To investigate the effect and safety of benzalkonium chloride on transscleral drug delivery in the rabbit after continuous intrascleral administration.METHODS. Betamethasone 21- phosphate ( BP) aqueous solutions, with or without benzalkonium chloride ( BAK), were continuously administered to albino rabbit sclera with an osmotic pump for 1 week. The BP concentrations in the aqueous humor, vitreous, and retina- choroid were measured by high-performance liquid chromatography ( HPLC). To investigate the effect of BAK on scleral permeability of BP in vitro, penetration of BP aqueous solution with or without BAK across the rabbit sclera was evaluated using a two- chamber Ussing apparatus. To determine the effects of BAK on transscleral delivery of large molecules, 20- and 70- kDa fluorescein isothiocyanate ( FITC)- dextran ( FD- 20 and - 70, respectively) aqueous solutions, with or without BAK, were continuously administered to the sclera by an osmotic pump. The intensity of fluorescence in the aqueous humor, vitreous, and retina- choroid was measured by fluorescence spectrophotometry at 1 week after implantation of the pump. The retinal toxicity of BAK was evaluated electrophysiologically and histologically.RESULTS. BAK increased concentrations of BP in the vitreous and retina- choroid compared with the control. BP was not detected in the aqueous humor. In the in vitro study, BAK did not increase the scleral permeability of BP. In the retina- choroid, BAK significantly increased concentrations of FD- 20 but did not increase those of FD- 70. The addition of BAK did not increase concentrations of FD- 20 or - 70 in the vitreous. No substantial toxic reactions were observed in the retina in electrophysiological or histologic examinations after the addition of BAK.CONCLUSIONS. The results of this study demonstrate that BAK may improve the ocular penetration of a drug in a transscleral drug delivery system without producing toxic reactions.