Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Int J Pharm. 2009 Dec 1;382(1-2):73-9. doi: 10.1016/j.ijpharm.2009.08.012. Epub 2009 Aug 15.
Differential scanning calorimetry was used to study the interaction of acyclovir and its prodrug squalenoyl-acyclovir (obtained by conjugation of 1,1',2-tris-nor-squalene acid (squaleneCOOH) with acyclovir) with biomembrane models made of DMPC multilamellar vesicles with the aim to verify whether a stronger interaction of the prodrug with respect to the free drug can be obtained. Multilamellar vesicles were prepared in the presence of increasing molar fractions of acyclovir, squaleneCOOH or prodrug and the effect of the compounds on the thermotropic behavior of vesicles was researched, revealing no effect of acyclovir but a strong effect of squaleneCOOH and prodrug. To evaluate if acyclovir, squaleneCOOH and prodrug can be absorbed by the biomembrane model, an experiment was carried out in which the considered compounds were left in contact with the biomembrane model and their eventual uptake was evaluated analyzing the effect on the thermotropic behavior of the biomembrane model. A very small uptake was revealed for all the compounds. To check the potential use of liposomes as a delivery system for the prodrug, the biomembrane models were incubated with liposomes loaded with the compounds and the compounds transferring from the loaded liposomes to the unloaded biomembrane model was followed. The results suggest that liposomes could be used to deliver the squalenoyl-acyclovir to the biomembrane model.
差示扫描量热法用于研究阿昔洛韦及其前药鲨烯酰基阿昔洛韦（通过将 1,1',2-三-nor-鲨烯酸（鲨烯酸 COOH）与阿昔洛韦缀合而获得）与由 DMPC 多层囊泡制成的生物膜模型的相互作用，目的是验证前药与游离药物相比是否可以获得更强的相互作用。在存在阿昔洛韦、鲨烯酸 COOH 或前药的摩尔分数逐渐增加的情况下制备多层囊泡，并研究了这些化合物对囊泡热致行为的影响，结果表明阿昔洛韦没有影响，但鲨烯酸 COOH 和前药有强烈影响。为了评估阿昔洛韦、鲨烯酸 COOH 和前药是否可以被生物膜模型吸收，进行了一项实验，其中将考虑的化合物与生物膜模型接触，并通过分析对生物膜模型热致行为的影响来评估其吸收情况。所有化合物的吸收量都非常小。为了检查脂质体作为前药传递系统的潜在用途，将负载有化合物的脂质体孵育在生物膜模型上，并跟踪从负载脂质体向未负载生物膜模型转移的化合物。结果表明，脂质体可用于将鲨烯酰基阿昔洛韦递送至生物膜模型。
