Reading School of Pharmacy, University of Reading, Whiteknights, PO Box 224, Reading RG6 6AD, Berkshire, United Kingdom.
School of Pharmacy, The Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom.
Int J Pharm. 2018 Oct 25;550(1-2):123-129. doi: 10.1016/j.ijpharm.2018.08.034. Epub 2018 Aug 18.
Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties which allow it to adhere to mucosal tissues. In this work, we explored chemical modification of chitosan through its reaction with methacrylic anhydride to synthesise methacrylated derivative with the aim to improve its mucoadhesive properties. The reaction products were characterised using H NMR, FTIR and UV-Vis spectroscopy. H NMR and ninhydrin test were used to quantify the degree of methacrylation of chitosan. Turbidimetric analysis of the effect of pH on aqueous solubility of the polymers revealed that the highly methacrylated derivative remained turbid and its turbidity did not change from pH 3 to 9. However, solutions of native chitosan and its derivative with low methacrylation remained transparent at pH 6.5 and exhibited a rapid increase in turbidity at pH > 6.5. The mucoadhesive properties of chitosan and its methacrylated derivatives were evaluated using flow-through method combined with fluorescent microscopy with fluorescein sodium as a model drug. The retention of these polymers was evaluated on porcine bladder mucosa in vitro. The methacrylated derivatives exhibited greater ability to retain fluorescein sodium on the bladder mucosa compared to the parent chitosan. Toxicological studies using MTT assay with UMUC3 bladder cells show no significant differences in toxicity between chitosan and its methacrylated derivatives suggesting good biocompatibility of these novel mucoadhesive polymers.
壳聚糖是一种带正电荷的多糖，具有黏膜黏附特性，能够黏附在黏膜组织上。在这项工作中，我们通过壳聚糖与甲基丙烯酰酐反应，探索了壳聚糖的化学修饰，以合成具有改善黏膜黏附特性的甲基丙烯酰化衍生物。使用 1H NMR、FTIR 和 UV-Vis 光谱对反应产物进行了表征。1H NMR 和茚三酮试验用于定量壳聚糖的甲基丙烯酰化程度。聚合物水溶液的 pH 值对其溶解度的浊度分析表明，高度甲基丙烯酰化的衍生物仍然混浊，其浊度从 pH 3 到 9 不变。然而，低甲基丙烯酰化的天然壳聚糖及其衍生物的溶液在 pH 6.5 下保持透明，并在 pH 值大于 6.5 时迅速增加浊度。使用荧光素钠作为模型药物，通过流动法结合荧光显微镜评估壳聚糖及其甲基丙烯酰化衍生物的黏膜黏附特性。在体外猪膀胱黏膜上评估这些聚合物的保留情况。与母体壳聚糖相比，甲基丙烯酰化衍生物在膀胱黏膜上保留荧光素钠的能力更强。使用 UMUC3 膀胱细胞的 MTT 测定进行的毒理学研究表明，壳聚糖及其甲基丙烯酰化衍生物之间的毒性没有显著差异，表明这些新型黏膜黏附聚合物具有良好的生物相容性。
