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用于药物递送的β-环糊精接枝β-马来酰壳聚糖纳米粒的制备与表征

Preparation and characterization of -cyclodextrin grafted -maleoyl chitosan nanoparticles for drug delivery.

作者信息

Hou Xinyu, Zhang Wenjuan, He Muye, Lu Yiben, Lou Kaiyan, Gao Feng

机构信息

Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China.

Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Asian J Pharm Sci. 2017 Nov;12(6):558-568. doi: 10.1016/j.ajps.2017.07.007. Epub 2017 Jul 25.

DOI:10.1016/j.ajps.2017.07.007
PMID:32104369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7032088/
Abstract

-cyclodextrin (CD) grafted N-maleoyl chitosan (CDNMCS) with two different degrees of substitution (DS) of -maleoyl (DS = 21.2% and 30.5%) were synthesized from maleic anhydride and chitosan bearing pendant cyclodextrin (CDCS). CDNMCS based nanoparticles were prepared via an ionic gelation method together with chitosan and CDCS nanoparticles. The size and zeta potential of prepared CDNMCS nanoparticles were 179.2274.0 nm and 36.242.4 mV, respectively. stability test indicated that CDNMCS nanoparticles were more stable in phosphate-buffered saline compared with chitosan nanoparticles. Moreover, a poorly water-soluble drug, ketoprofen (KTP), was selected as a model drug to study the obtained nanoparticle's potentials as drug delivery carriers. The drug loading efficiency of CDNMCS20 nanoparticles were 14.8% for KTP. MTT assay showed that KTP loaded CDNMCS nanoparticles were safe drug carriers. Notably, drug release studies showed that KTP was released in a sustained-release manner for the nanoparticles. The pharmacokinetic of drug loaded CDNMCS20 nanoparticles were evaluated in rats after intravenous administration. The results of studies revealed that, compared with free KTP, KTP loaded CDNMCS20 nanoparticles exhibited a significant increase in AUC and mean residence time by 6.6-fold and 2.9-fold, respectively. Therefore, CDNMCS nanoparticles could be used as a novel promising nanoparticle-based drug delivery system for sustained release of poorly water-soluble drugs. The carboxylic acid groups of the CDNMCS molecule provide convenient sites for further structural modifications including introduction of tissue- or disease- specific targeting groups.

摘要

以马来酸酐和带有环糊精侧链的壳聚糖（CDCS）为原料，合成了具有两种不同马来酰化取代度（DS = 21.2%和30.5%）的β-环糊精（CD）接枝N-马来酰壳聚糖（CDNMCS）。通过离子凝胶法，与壳聚糖和CDCS纳米颗粒一起制备了基于CDNMCS的纳米颗粒。所制备的CDNMCS纳米颗粒的尺寸和zeta电位分别为179.2274.0 nm和36.242.4 mV。稳定性测试表明，与壳聚糖纳米颗粒相比，CDNMCS纳米颗粒在磷酸盐缓冲盐水中更稳定。此外，选择一种难溶性药物酮洛芬（KTP）作为模型药物，研究所得纳米颗粒作为药物递送载体的潜力。CDNMCS20纳米颗粒对KTP的载药效率为14.8%。MTT法表明，负载KTP的CDNMCS纳米颗粒是安全的药物载体。值得注意的是，药物释放研究表明，KTP从纳米颗粒中以缓释方式释放。静脉给药后，在大鼠体内评估了负载药物的CDNMCS20纳米颗粒的药代动力学。研究结果显示，与游离KTP相比，负载KTP的CDNMCS20纳米颗粒的AUC和平均驻留时间分别显著增加了6.6倍和2.9倍。因此，CDNMCS纳米颗粒可作为一种新型的、有前景的基于纳米颗粒的药物递送系统，用于难溶性药物的缓释。CDNMCS分子的羧酸基团为进一步的结构修饰提供了便利位点，包括引入组织或疾病特异性靶向基团。

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