Krasota A, Belousova R, Duchêne D, Larionova N
Scryabin Moscow Veterinary Medicine Academy, 109472, Moscow, Russia.
J Control Release. 2002 Dec 13;85(1-3):117-24. doi: 10.1016/s0168-3659(02)00287-0.
This study evaluated the antiviral effect of various dosage forms of proteinase inhibitor-aprotinin as a potential remedy for prophylactics and therapy of infectious bovine rhinotracheitis. Formulations of the inhibitor were tested for their influence on bovine herpes virus reproduction in cell cultures. Starch/bovine serum albumin microcapsules with aprotinin were prepared using interfacial cross-linking with terephthaloyl chloride and characterized for their morphology, size and release of the inhibitor. Two types of these microcapsules-impregnated and loaded with the inhibitor-were used in virus infectious studies. Native aprotinin possessed palpable dose-dependent antiviral effect inhibiting the virus reproduction up to 4.0 lg (10000-fold) and delaying the cytopathic effect up to 96 h in the concentration 800-3300 TIU/ml. The bioadhesive, biodegradable aprotinin-loaded microcapsules were the most effective antiviral drug as this formulation allowed to decrease virus infectious titer up to 4.0 lg and a delay in the cytopathic effect of up to 144 h in lesser doses of inhibitor compared with the native form. In comparison the antiviral effect of microcapsules impregnated with aprotinin was not so appreciable. It was interesting to note that the results of the experiments on diverse cultures were very similar. This was because the drugs influenced the fundamental processes of virus replication cycle.
本研究评估了蛋白酶抑制剂抑肽酶的各种剂型作为传染性牛鼻气管炎预防和治疗潜在药物的抗病毒效果。测试了该抑制剂的制剂对细胞培养中牛疱疹病毒繁殖的影响。使用对苯二甲酰氯通过界面交联制备了含有抑肽酶的淀粉/牛血清白蛋白微胶囊,并对其形态、大小和抑制剂释放进行了表征。在病毒感染研究中使用了两种类型的这种微胶囊——浸渍型和负载型。天然抑肽酶具有明显的剂量依赖性抗病毒作用,在800 - 3300 TIU/ml的浓度下,可抑制病毒繁殖达4.0 lg(10000倍),并将细胞病变效应延迟达96小时。生物黏附、可生物降解的负载抑肽酶微胶囊是最有效的抗病毒药物,因为与天然形式相比,这种制剂在较低剂量的抑制剂下就能使病毒感染滴度降低达4.0 lg,并将细胞病变效应延迟达144小时。相比之下,浸渍有抑肽酶的微胶囊的抗病毒效果不太明显。值得注意的是,在不同培养物上的实验结果非常相似。这是因为这些药物影响了病毒复制周期的基本过程。