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Abstract：
The objective was to investigate (trans)corneal and transscleral iontophoresis of biolabile amino acid ester prodrugs of aciclovir (ACV-X, X = Arg, Gly and Trp) as a means to increase ocular bioavailability of ACV. Prodrugs displayed tissue-dependent susceptibility to hydrolysis. Iontophoresis of ACV-Arg, ACV-Gly and ACV-Trp (5 mM, 0.5 mA/cm2) for 5 min followed by 55 min passive diffusion resulted in appreciable corneal deposition (21.5 ± 5.1, 14.1 ± 2.0 and 5.3 ± 0.6 nmol/cm2, respectively) and transcorneal permeation (13.9 ± 1.6, 10.9 ± 1.8 and 5.7 ± 0.5 nmol/cm2, respectively) of ACV species. In contrast, passive delivery of ACV across porcine cornea after 1 h was < LOQ (i.e. <0.125 nmol/cm2). Transscleral permeation of ACV-Arg, ACV-Gly and ACV-Trp (9 mM, 1.25 mA/cm2) after iontophoresis for 5 min was 20.4 ± 3.8, 12.3 ± 0.3 and 8.4 ± 0.4 nmol/cm2, respectively - far superior to passive delivery which was again < LOQ. Using intact porcine eye globes, 5 min transscleral iontophoresis of ACV-Gly at 3.75 mA/cm2 resulted in considerable delivery of ACV species to the choroid/retina and vitreous humour (5.7 ± 2.3 and 11.7 ± 3.7 nmol/cm2, respectively). Furthermore, the average concentration of ACV species in the whole eyeball (4.5 ± 1.6 nmol/cm3) was significantly higher than the IC50 of ACV against HSV-1 (<0.22 nmol/cm3), demonstrating the potential application for the treatment of ocular HSV infections.
摘要：
目的是研究阿昔洛韦生物不稳定氨基酸酯前药（ACV-X，X=Arg,Gly和Trp）作为增加ACV的眼部生物利用度的手段。前药表现出对水解的组织依赖性敏感性。ACV-Arg离子电渗疗法,ACV-Gly和ACV-Trp（5mM，0.5mA/cm2）持续5分钟，然后进行55分钟的被动扩散导致明显的角膜沉积（分别为21.5±5.1、14.1±2.0和5.3±0.6nmol/cm2）和角膜渗透（分别为13.9±1.6、10.9±1.8和5.7±0.5nmol/cm2）。相比之下,1小时后通过猪角膜被动递送ACV
