Nagai Noriaki, Mano Yu, Ito Yoshimasa
Faculty of Pharmacy, Kindai University.
Biol Pharm Bull. 2016;39(11):1881-1887. doi: 10.1248/bpb.b16-00592.
Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension. The nano-DSF suspension was prepared by a bead mill method to yield a mean particle size of nano-DSF of 181 nm. Following the instillation of 1.4% DSF solution or the nano-DSF suspension, DDC was detected only in the aqueous humor and lens; in both, the area under the curve (AUC) and mean residence time (MRT) for the nano-DSF suspension were higher than for the DSF solution. In addition, we found that the DDC residence time in the cortex and nucleus of the lens was higher than in the capsule-epithelium. Although DDC was not detected in the cortex and nucleus of lenses following the instillation of the 1.4% DSF solution, the instillation of a 1.4% nano-DSF suspension led to the accumulation of DDC in both areas. In conclusion, it is possible that the instillation of a nano-DSF suspension can supply more DDC into the aqueous humor and lens than a conventional formulation, and these findings provide information significant for the prevention of cataracts and the design of a lens targeted drug delivery system.
双硫仑（DSF）是二乙基二硫代氨基甲酸盐（DDC）的二聚体，我们之前将其添加到2-羟丙基-β-环糊精溶液中（DSF溶液）。我们发现，向遗传性白内障ICR/f大鼠滴注这种DSF溶液可延缓晶状体混浊。在本研究中，我们试图设计一种含有DSF纳米颗粒的眼科制剂，用作晶状体靶向给药系统（纳米DSF混悬液），并研究滴注DSF溶液或纳米DSF混悬液后晶状体中药物含量的变化。通过珠磨法制备纳米DSF混悬液，使纳米DSF的平均粒径为181nm。滴注1.4%的DSF溶液或纳米DSF混悬液后，仅在房水和晶状体中检测到DDC；两者中，纳米DSF混悬液的曲线下面积（AUC）和平均驻留时间（MRT）均高于DSF溶液。此外，我们发现DDC在晶状体皮质和核中的驻留时间高于囊膜-上皮。虽然滴注1.4%的DSF溶液后在晶状体皮质和核中未检测到DDC，但滴注1.4%的纳米DSF混悬液导致DDC在这两个区域均有积累。总之，滴注纳米DSF混悬液可能比传统制剂向房水和晶状体中提供更多的DDC，这些发现为预防白内障和设计晶状体靶向给药系统提供了重要信息。
