Jarvis Chris A, McGuigan Chris, Heard Charles M
Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
Pharm Res. 2004 Jun;21(6):914-9. doi: 10.1023/b:pham.0000029277.60760.43.
To determine the in-vitro dermal delivery of a new class of lipophilic, highly potent and uniquely selective anti-VZV nucleoside analogues in comparison with aciclovir.
Three test compounds (Cf1698, Cf1743, Cf1712) and aciclovir were formulated into propylene glycol/aqueous cream BP formulations and finite doses applied to full-thickness pig ear skin for 48 hours in vertical Franz-type diffusion cells. Receptor phase samples were taken at specific intervals to determine permeation, and depth profiles were constructed following tape stripping and membrane separation.
All three test compounds reached the target basal epidermis in concentrations suggesting they would be highly efficacious in reducing viral load. Furthermore, the data showed that each of the test compounds would perform in a far superior manner to aciclovir, the current treatment of choice.
The dermatomal site of viral replication during secondary infection--the basal epidermis--was successfully targeted. Topical delivery of these compounds is highly promising as a new first line treatment of VZV infections. By attacking the virus at the first sign of reactivation, it is proposed that the extent of damage caused by the virus would be significantly lowered, thereby limiting the extent and severity of post-herpetic neuralgia.
与阿昔洛韦相比，确定一类新型亲脂性、高效且具有独特选择性的抗水痘带状疱疹病毒（VZV）核苷类似物的体外皮肤递送情况。
将三种受试化合物（Cf1698、Cf1743、Cf1712）和阿昔洛韦配制成丙二醇/水性乳膏英国药典制剂，并在垂直的弗兰兹型扩散池中以有限剂量施用于猪耳全层皮肤48小时。在特定时间间隔采集受体相样品以测定渗透情况，并在胶带剥离和膜分离后构建深度分布曲线。
所有三种受试化合物均以表明它们在降低病毒载量方面将非常有效的浓度到达目标基底表皮。此外，数据表明每种受试化合物的表现都将远优于目前的首选治疗药物阿昔洛韦。
成功靶向了继发感染期间病毒复制的皮节部位——基底表皮。这些化合物的局部递送作为VZV感染的一种新的一线治疗方法具有很大的前景。通过在病毒重新激活的最初迹象时攻击病毒，有人提出病毒造成的损伤程度将显著降低，从而限制带状疱疹后神经痛的程度和严重程度。
