季铵改性右旋糖酐：一种独特的可生物降解粘接聚合物

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-06-23 DOI:10.1016/j.ejpb.2025.114788

Khush Bakhat Afzal , Gergely Kali , Muhammad Haris , Marlene Ramona Schmidt , Melanie Ebert , Eduard Stefan , Andreas Bernkop-Schnürch

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引用次数: 0

摘要

目的制备一种具有良好黏附性能和高生物相容性的阳离子葡聚糖聚合物。方法采用n -氯甜菜碱酯化法制备季铵盐改性右旋糖酐。结构表征，如zeta电位测量、酯定量、核磁共振、红外光谱和酶降解研究，以确认季铵结构与右旋糖酐主链的共价连接。通过体外HeLa和Caco-2细胞毒性分析和溶血试验评价改性葡聚糖的生物相容性。利用平板流变仪研究了改性右旋糖酐与猪黏液的相互作用。研究了猪粘膜的黏附性能。结果以640.4±9.051µmol/g酯为原料，季铵修饰右旋糖酐的zeta电位由- 25.4±0.5 mV转变为+ 15.6±0.7 mV。核磁共振和红外光谱分析证实了季铵基团与聚合物主链的共价结合。酶降解研究证实了脂肪酶介导的对改性右旋糖酐季铵部分的裂解。细胞毒性和溶血实验结果表明，季铵修饰右旋糖酐在0.5%浓度下无毒性。季铵改性右旋糖酐与黏液在3 h和6 h时的动态粘度分别比天然聚合物高2.1倍和3.6倍。此外，与天然葡聚糖相比，季铵修饰的葡聚糖对肠道粘膜的黏附性能提高了3.4倍。结论季铵修饰右旋糖酐具有良好的阳离子特性，具有良好的黏附性能和良好的生物相容性。

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Quaternary ammonium-modified dextran: a unique biodegradable mucoadhesive polymer

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Quaternary ammonium-modified dextran: a unique biodegradable mucoadhesive polymer

Aim

The present study aims to develop a cationic dextran polymer with improved mucoadhesive properties and high biocompatibility.

Methodology

Quaternary ammonium-modified dextran was synthesized of dextran via esterification with N-chlorobetainyl chloride. Structural characterizations like zeta potential measurements, ester quantification, NMR, FTIR, and enzymatic degradation studies were performed to confirm the covalent attachment of quaternary ammonium structure to dextran backbone. Biocompatibility of modified dextran was evaluated by in vitro cytotoxic analysis on HeLa and Caco-2 cells, and hemolysis assay. Furthermore, interaction of modified dextran with porcine mucus was evaluated by using plate rheometer. Mucoadhesive properties were investigated on porcine mucosa mimicking in vivo conditions.

Results

A shift in zeta potential from −25.4 ± 0.5 to + 15.6 ± 0.7 mV was obtained for quaternary ammonium-modified dextran with 640.4 ± 9.051 µmol/g ester content. NMR and FTIR analysis confirmed the covalent binding of quaternary ammonium moieties to the polymer backbone. Enzymatic degradation studies demonstrated the lipase-mediated cleavage of quaternary ammonium moieties from modified dextran. Cytotoxicity and hemolysis results proved that quaternary ammonium-modified dextran was not toxic up to the concentration of 0.5 %. Rheometric measurements of quaternary ammonium-modified dextran with mucus showed 2.1- and 3.6-fold higher dynamic viscosity than native polymer at 3 h and 6 h time intervals, respectively. Moreover, compared to native dextran, quaternary ammonium-modified dextran showed 3.4-fold higher mucoadhesive properties on the intestinal mucosa.

Conclusion

Because of its cationic character, quaternary ammonium-modified dextran exhibits promising potential as a biodegradable polymer with improved mucoadhesive properties and remarkable biocompatibility.

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来源期刊

European Journal of Pharmaceutics and Biopharmaceutics 医学-药学

CiteScore

8.80

自引率

4.10%

发文量

211

审稿时长

36 days

期刊介绍： The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.