Saettone M F, Monti D, Torracca M T, Chetoni P
Laboratory of Pharmaceutical Technology/Biopharmaceutics, University of Pisa, Italy.
J Ocul Pharmacol. 1994 Spring;10(1):83-92. doi: 10.1089/jop.1994.10.83.
A series of polyanionic natural or semi-synthetic polymers (polygalacturonic acid, hyaluronic acid, carboxymethylamylose, carboxymethylchitin, chondroitin sulfate, heparan sulfate and mesoglycan) were evaluated as potential mucoadhesive carriers for ophthalmic drugs. Solutions containing cyclopentolate (CY) or pilocarpine (PI) as salts (or polyanionic complexes) with the acidic polymers, all showing a low viscosity, were tested for miotic (resp. mydriatic) activity in albino rabbits. In the case of some polymeric complexes, small but significant increases of the areas under the activity vs. time curves (AUC) over reference cyclopentolate hydrochloride (CYHC1) or pilocarpine nitrate (PINO3) vehicles, and significant AUC decreases after removal of precorneal mucin by treatment with N-acetylcysteine were observed. A correlation was found between these data, considered indicative of the occurrence of a mucoadhesive interaction "in vivo", and "in vitro" viscometric data expressing the polymers-mucin force of interaction. The advantages and limitations of the mucoadhesive non-viscous approach in the formulation of ophthalmic vehicles are presented and discussed.
评估了一系列聚阴离子天然或半合成聚合物（聚半乳糖醛酸、透明质酸、羧甲基直链淀粉、羧甲基几丁质、硫酸软骨素、硫酸乙酰肝素和葡糖胺聚糖）作为眼科药物潜在的粘膜粘附载体。测试了含有环喷托酯（CY）或毛果芸香碱（PI）作为与酸性聚合物形成的盐（或聚阴离子复合物）的溶液，所有溶液粘度均较低，以检测其对白化兔的缩瞳（或散瞳）活性。对于一些聚合物复合物，与对照环喷托酯盐酸盐（CYHCl）或硝酸毛果芸香碱（PINO3）载体相比，活性-时间曲线下面积（AUC）有小幅但显著增加，在用N-乙酰半胱氨酸处理去除角膜前粘液后，AUC显著降低。发现这些数据之间存在相关性，这些数据被认为表明“体内”发生了粘膜粘附相互作用，与表达聚合物-粘蛋白相互作用力的“体外”粘度数据相关。本文介绍并讨论了粘膜粘附非粘性方法在眼科药物载体制剂中的优点和局限性。
