Wang Siling, Li Dexin, Ito Yoshimasa, Nabekura Tomohiro, Wang Shujun, Zhang Jinghai, Wu Chunfu
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110-016, China.
Curr Eye Res. 2004 Jul;29(1):51-8. doi: 10.1080/02713680490513209.
To test the effect of aqueous eye drops containing a high concentration of disulfiram (DSF) in a cyclodextrin- based drug delivery system. This system increases both the drug solubility in aqueous eye drops and the permeability of drug into the rabbit eye, by the formation of a drug-cyclodextrin inclusion complex, and so enhances the ocular bioavailability and anti-cataract effect of DSF.
The DSF and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion (DSF/HPbetaCD) was studied using solubility methods, IR spectra and X-ray diffraction patterns. Suitable formulations for DSF eye drops were first identified by a trans-corneal penetration experiment in vitro. Finding a new p-bromophenacyl bromide (p-BPB) derivative reagent for diethyldithiocarbamic acid (DDC), which was a metabolite of DSF, allowed precise determination of the contents of DSF in aqueous humor. The ocular bioavailability was calculated by a transcorneal experiment of DSF in vivo. The lens opacity of a selenite-induced cataract in rat pups was monitored using a slit lamp with an anterior eye segment analysis system.
The formation of DSF/HPbetaCD inclusion and the addition of hydroxypropylmethylcellulose (HPMC), as a penetration enhancer, played very important roles in increasing the ocular bioavailability of DSF. DSF eye drops, with a formulation of 1.26% (w/v) DSF/HPbetaCD inclusion, 0.01% (w/v) HPMC, 0.005% (w/v) benzalkonium chloride and 0.9% (w/v) sodium chloride, inhibited the onset of selenite-induced cataracts effectively.
The cyclodextrin-based drug delivery system enhances both the solubility of DSF in aqueous eye drops and permeability of the drug into the rabbit eye. DSF ocular bioavailability in rabbit aqueous humor exceeded those reported for the DSF ophthalmic preparation. DSF eye drops effectively prevent the development of selenite-induced cataracts.
测试基于环糊精的药物递送系统中含高浓度双硫仑（DSF）的水性滴眼液的效果。该系统通过形成药物 - 环糊精包合物，提高了药物在水性滴眼液中的溶解度以及药物进入兔眼的渗透率，从而增强了DSF的眼部生物利用度和抗白内障效果。
采用溶解度方法、红外光谱和X射线衍射图谱研究了DSF与羟丙基 - β - 环糊精（HPβCD）的包合物（DSF/HPβCD）。首先通过体外角膜渗透实验确定适合DSF滴眼液的配方。找到一种用于二乙基二硫代氨基甲酸（DDC，DSF的代谢产物）的新的对溴苯甲酰溴（p - BPB）衍生试剂，能够精确测定房水中DSF的含量。通过DSF的体内角膜实验计算眼部生物利用度。使用带有眼前节分析系统的裂隙灯监测亚硒酸盐诱导的大鼠幼崽白内障的晶状体混浊情况。
DSF/HPβCD包合物的形成以及作为渗透促进剂的羟丙基甲基纤维素（HPMC）的添加，在提高DSF的眼部生物利用度方面发挥了非常重要的作用。配方为1.26%（w/v）DSF/HPβCD包合物、0.01%（w/v）HPMC、0.005%（w/v）苯扎氯铵和0.9%（w/v）氯化钠的DSF滴眼液能有效抑制亚硒酸盐诱导的白内障的发生。
基于环糊精的药物递送系统提高了DSF在水性滴眼液中的溶解度以及药物进入兔眼的渗透率。兔房水中DSF的眼部生物利用度超过了已报道的DSF眼用制剂的生物利用度。DSF滴眼液能有效预防亚硒酸盐诱导的白内障的发展。
