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用于热响应和pH响应药物释放的MIL-125(Ti)载体的从头合成。

De novo synthesis of a MIL-125(Ti) carrier for thermal- and pH-responsive drug release.

作者信息

Lin You-Sheng, Lin Kuen-Song, Mdlovu Ndumiso Vukile, Weng Meng-Tzu, Tsai Wei-Chin, Jeng U-Ser

机构信息

Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li District, Taoyuan City 32003, Taiwan.

Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li District, Taoyuan City 32003, Taiwan.

出版信息

Biomater Adv. 2022 Sep;140:213070. doi: 10.1016/j.bioadv.2022.213070. Epub 2022 Aug 5.

Abstract

Microporous round cake-like (diameter: 900 ± 100 nm) MIL-125(Ti) carrier with a central metal (Ti) exhibiting bio-affinity and possessing a great potential to be used as drug release platform, has been synthesized in the present study. The thermal and pH responsiveness of drug delivery systems (DDS) are the most important parameters for drug release and can be provided through polymer coating techniques. The Pluronic F127 (F127) and chitosan (CH) monomers were inserted into the crystal lattice of MIL-125(Ti) carrier during the de novo synthesis process, which were subsequently loaded with doxorubicin (DOX). The results reveal particle size changes (ranged between 30 and 50 %) from the original size of the MIL-125(Ti) carrier in response to temperature and pH when the carrier reaches acid environment. The drug release profiles have been completed through self-design device, which provides for the real-time release in the DOX amounts via UV-Vis spectra. The kinetics analysis was used to evaluate the R values of first order, Higuchi, Korsmeyer-peppas, and Weibull fitting equations, where the Weibull fitting indicated the best R. An increase by 59.3 % of DOX released under the acid status (pH = 5.4) was observed, indicating that the CH-MIL-125(Ti) carrier is temperature and pH responsive. Moreover, the lattice explosion resulting from the temperature increase in the range of 25-42 °C caused an increase in F127-MIL-125(Ti) by 30.8-38.3 %. The simulated SAXS/WAXS studies for the microstructures of MIL-125(Ti) based DDS at different temperatures after polymer coating (F127-MIL-125(Ti)) provide the possible mechanism of lattice explosion. As such, the responsive Ti-MOF has a highly potential for use in the applications of cancer treatment.

摘要

本研究合成了具有生物亲和力且有很大潜力用作药物释放平台的微孔圆形饼状(直径:900±100nm)MIL-125(Ti)载体,其中心金属(Ti)具有生物亲和力。药物递送系统(DDS)的热响应性和pH响应性是药物释放的最重要参数,可通过聚合物包衣技术实现。在从头合成过程中,将普朗尼克F127(F127)和壳聚糖(CH)单体插入到MIL-125(Ti)载体的晶格中,随后负载阿霉素(DOX)。结果表明,当载体处于酸性环境时,响应温度和pH,MIL-125(Ti)载体的原始尺寸粒径变化(范围在30%至50%之间)。药物释放曲线通过自行设计的装置完成,该装置通过紫外可见光谱实时释放DOX量。动力学分析用于评估一级、Higuchi、Korsmeyer-peppas和Weibull拟合方程的R值,其中Weibull拟合显示最佳R值。观察到在酸性状态(pH = 5.4)下DOX释放增加了59.3%,表明CH-MIL-125(Ti)载体具有温度和pH响应性。此外,在25-42°C范围内温度升高导致晶格爆炸,使F127-MIL-125(Ti)增加了30.8-38.3%。对聚合物包衣(F127-MIL-125(Ti))后不同温度下基于MIL-125(Ti)的DDS微观结构进行的模拟SAXS/WAXS研究提供了晶格爆炸的可能机制。因此,这种响应性Ti-MOF在癌症治疗应用中具有很高的潜力。

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