Yessine Marie-Andrée, Leroux Jean-Christophe
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
Adv Drug Deliv Rev. 2004 Apr 23;56(7):999-1021. doi: 10.1016/j.addr.2003.10.039.
Water-soluble synthetic polyanions are employed nowadays in a multitude of industrial and biomedical applications and are studied extensively as simplified models of natural polyelectrolytes. The most interesting feature of carboxylated polymers is undoubtedly their ability to undergo coil-to-globule conformational change upon a decrease in pH of the surrounding environment. Over the years, scientists have gained better insights into the conformational behavior of these polymers in solution and in the presence of membrane bilayers. In addition, when used as protein models, anionic polyelectrolytes can provide valuable information on physiological processes such as domain formation in biological membranes. Recently, polyanions have been evaluated as part of drug delivery systems, either as complexes/conjugates with biomolecules, or in the preparation of pH-sensitive liposomal formulations. This article reviews the fundamental and practical aspects of pH-responsive synthetic polyanions in drug delivery. The pH-dependent conformational behavior of these polymers in aqueous solution is described in detail using poly(methacrylic acid) as the model polymer. Since binding to cellular membranes is a fundamental issue in understanding the mechanism of action of polyanions in cytoplasmic drug delivery, studies characterizing their interactions with phospholipid bilayers at neutral as well as at acidic pH are reviewed. Finally, pH-responsive delivery systems based on these polymers are described. As the conformational properties of pH-sensitive polyanions can be easily modulated by carefully adjusting their composition, such formulations may represent an attractive strategy to improve the escape of active biomolecules from acidic endosomal compartments.
水溶性合成聚阴离子如今被广泛应用于众多工业和生物医学领域，并作为天然聚电解质的简化模型被深入研究。羧化聚合物最有趣的特性无疑是其在周围环境pH值降低时能够发生从线圈状到球状的构象变化。多年来，科学家们对这些聚合物在溶液中和存在膜双层时的构象行为有了更深入的了解。此外，当用作蛋白质模型时，阴离子聚电解质可以提供有关生理过程的有价值信息，例如生物膜中的结构域形成。最近，聚阴离子已被评估为药物递送系统的一部分，要么作为与生物分子的复合物/共轭物，要么用于制备pH敏感的脂质体制剂。本文综述了pH响应性合成聚阴离子在药物递送中的基本和实际方面。以聚（甲基丙烯酸）为模型聚合物，详细描述了这些聚合物在水溶液中的pH依赖性构象行为。由于与细胞膜的结合是理解聚阴离子在细胞质药物递送中作用机制的一个基本问题，因此综述了在中性和酸性pH下表征它们与磷脂双层相互作用的研究。最后，描述了基于这些聚合物的pH响应递送系统。由于可以通过仔细调整其组成轻松调节pH敏感聚阴离子的构象性质，此类制剂可能代表一种有吸引力的策略，以改善活性生物分子从酸性内体区室的逃逸。
