Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Torino, Italy.
Eur J Pharm Biopharm. 2012 Jan;80(1):39-45. doi: 10.1016/j.ejpb.2011.10.001. Epub 2011 Oct 8.
The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4'-trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4'-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug. Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug.
本研究旨在通过眼部给药途径提高抗病毒药物阿昔洛韦（ACV）的生物利用度。为此，合成了一种新的阿昔洛韦亲脂性衍生物，该衍生物具有更高的亲脂性，并能形成均一水分散体，比母体药物的水溶液中含有更高量的 ACV。这是通过将阿昔洛韦化学连接到角鲨烯的异戊二烯链上来实现的，得到 4'-三异戊烯酰基阿昔洛韦（SQACV），其中角鲨烯与阿昔洛韦的 4'-羟基共价结合。然后，通过纳米沉淀将这种新的前药配制成非聚合纳米组装体；对所得颗粒的平均粒径、Zeta 电位和稳定性进行了表征。评估了前药在兔泪液和房水中的药代动力学特征，并与母体药物进行了比较。数据表明，与游离 ACV 溶液相比，SQACV 纳米组装体增加了兔房水中的 ACV 含量。阿昔洛韦的这种新的两亲性前药是提高母体药物眼部生物利用度的很有前途的工具。
