Jones David S, Laverty Thomas P, Morris Caoimhe, Andrews Gavin P
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, United Kingdom.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, United Kingdom.
Colloids Surf B Biointerfaces. 2016 Aug 1;144:125-134. doi: 10.1016/j.colsurfb.2016.03.008. Epub 2016 Mar 4.
Poly(methylvinylether-co-maleic acid) (PMVE/MA) is commonly used as a component of pharmaceutical platforms, principally to enhance interactions with biological substrates (mucoadhesion). However, the limited knowledge on the rheological properties of this polymer and their relationships with mucoadhesion has negated the biomedical use of this polymer as a mono-component platform. This study presents a comprehensive study of the rheological properties of aqueous PMVE/MA platforms and defines their relationships with mucoadhesion using multiple regression analysis. Using dilute solution viscometry the intrinsic viscosities of un-neutralised PMVE/MA and PMVE/MA neutralised using NaOH or TEA were 22.32±0.89dLg(-1), 274.80±1.94dLg(-1) and 416.49±2.21dLg(-1) illustrating greater polymer chain expansion following neutralisation using Triethylamine (TEA). PMVE/MA platforms exhibited shear-thinning properties. Increasing polymer concentration increased the consistencies, zero shear rate (ZSR) viscosities (determined from flow rheometry), storage and loss moduli, dynamic viscosities (defined using oscillatory analysis) and mucoadhesive properties, yet decreased the loss tangents of the neutralised polymer platforms. TEA neutralised systems possessed significantly and substantially greater consistencies, ZSR and dynamic viscosities, storage and loss moduli, mucoadhesion and lower loss tangents than their NaOH counterparts. Multiple regression analysis enabled identification of the dominant role of polymer viscoelasticity on mucoadhesion (r>0.98). The mucoadhesive properties of PMVE/MA platforms were considerable and were greater than those of other platforms that have successfully been shown to enhance in vivo retention when applied to the oral cavity, indicating a positive role for PMVE/MA mono-component platforms for pharmaceutical and biomedical applications.
聚（甲基乙烯基醚-马来酸共聚物）（PMVE/MA）通常用作药物平台的一种成分，主要用于增强与生物底物的相互作用（粘膜粘附）。然而，关于这种聚合物的流变学性质及其与粘膜粘附关系的知识有限，这使得这种聚合物作为单一组分平台在生物医学领域的应用受到了限制。本研究全面研究了PMVE/MA水性平台的流变学性质，并使用多元回归分析确定了它们与粘膜粘附的关系。通过稀溶液粘度测定法，未中和的PMVE/MA以及用NaOH或TEA中和的PMVE/MA的特性粘度分别为22.32±0.89dLg(-1)、274.80±1.94dLg(-1)和416.49±2.21dLg(-1)，这表明用三乙胺（TEA）中和后聚合物链有更大程度的伸展。PMVE/MA平台表现出剪切变稀特性。聚合物浓度的增加提高了稠度、零剪切速率（ZSR）粘度（通过流动流变学测定）、储能模量和损耗模量、动态粘度（通过振荡分析定义）以及粘膜粘附性能，但降低了中和后的聚合物平台的损耗角正切。与用NaOH中和的体系相比，TEA中和的体系具有显著更高的稠度、ZSR和动态粘度、储能模量和损耗模量、粘膜粘附性以及更低的损耗角正切。多元回归分析能够确定聚合物粘弹性对粘膜粘附的主导作用（r>0.98）。PMVE/MA平台的粘膜粘附性能相当可观，并且大于其他已成功证明应用于口腔时能增强体内滞留的平台，这表明PMVE/MA单一组分平台在药物和生物医学应用中具有积极作用。
