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采用离子凝胶法制备含吲唑啉三环螺环氧化吲哚衍生物壳聚糖纳米粒的制备及特性研究

Development and characterization of chitosan nanoparticles containing an indanonic tricyclic spiroisoxazoline derivative using ion-gelation method: an study.

机构信息

Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.

Department of Chemical Engineering, University of Qom, Qom, Iran.

出版信息

Drug Dev Ind Pharm. 2020 Oct;46(10):1604-1612. doi: 10.1080/03639045.2020.1811304. Epub 2020 Sep 3.

DOI:10.1080/03639045.2020.1811304
PMID:32812474
Abstract

Biodegradable nanoparticulate carriers are potentially applicable compounds in the administration of therapeutic agents and drug delivery. They have received much attention due to their biological characteristics such as biodegradability, biocompatibility, and bioadhesive. The objectives of this work are first, investigating the impact of two important parameters (i.e. chitosan or sodium tripolyphosphate (TPP) solution concentration and chitosan to TPP mass ratio) on the chitosan nanoparticles (CNPs) formation by ionic-gelation method and then, the synthesis and characterization of chitosan-based, biodegradable drug-loaded nanoparticles in the encapsulation of novel 4'-(4-(methylsulfonyl)phenyl)-3'-(3,4,5-trimethoxyphenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one (MTS) indanonic tricyclic spiroisoxazoline, which is a potent anticancer drug. The particle size, shape, zeta potential, drug loading capacity, release characteristics, and stability of the formulated drug-loaded nanoparticles of the different drug:carrier ratio has been studied. The results indicated that the particle size increased at the higher chitosan or TPP concentration while the mass ratio did not appear to be a significant parameter during the cross-linking process. The particle diameter and zeta potential of CNPs including MTS were approximately in the range of 256-350 nm and 24.08-38.70 mV, respectively. The entrapment efficiency steadily increased with increasing the concentration of the polymer in formulizations. Throughout 24 h, the release behavior was provided a sustained release from all the drug-loaded formulizations. The optimal formulization of CNPs based on drug content with a drug:carrier ratio of 1:2 did not change appreciably during 60-day storage at either 4 °C or the ambient temperature.

摘要

可生物降解的纳米颗粒载体是治疗剂给药和药物递送中潜在适用的化合物。由于其生物特性,如可生物降解性、生物相容性和生物粘附性,它们受到了广泛关注。本工作的目的首先是研究两个重要参数(即壳聚糖或三聚磷酸钠(TPP)溶液浓度和壳聚糖与 TPP 质量比)对离子凝胶法形成壳聚糖纳米颗粒(CNPs)的影响,然后,合成并表征基于壳聚糖的、可生物降解的载药纳米颗粒,用于封装新型 4'-(4-(甲基磺酰基)苯基)-3'-(3,4,5-三甲氧基苯基)-4'H-螺[茚-2,5'-异恶唑]-1(3H)-酮(MTS)茚满并三环螺异恶唑啉,这是一种有效的抗癌药物。研究了不同药物:载体比的载药纳米颗粒的粒径、形状、Zeta 电位、载药量、释放特性和稳定性。结果表明,在较高的壳聚糖或 TPP 浓度下,粒径增加,而质量比在交联过程中似乎不是一个重要参数。载有 MTS 的 CNPs 的粒径和 Zeta 电位约为 256-350nm 和 24.08-38.70mV。包封效率随着聚合物浓度的增加而稳定增加。在 24h 内,所有载药配方均提供了持续释放。基于药物含量的 CNPs 的最佳配方,在 4°C 或环境温度下储存 60 天,药物:载体比为 1:2 时,其药物含量没有明显变化。

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