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负载地拉罗司纳米颗粒的热敏TMPO氧化木质纤维素/阳离子琼脂糖水凝胶用于黑色素瘤的光热治疗

Thermosensitive TMPO-oxidized lignocellulose/cationic agarose hydrogel loaded with deferasirox nanoparticles for photothermal therapy in melanoma.

作者信息

Veisi Hadis, Varshosaz Jaleh, Rostami Mahboubeh, Mirian Mina

机构信息

Novel Drug Delivery Systems Research Centre, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Novel Drug Delivery Systems Research Centre, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Int J Biol Macromol. 2023 May 31;238:124126. doi: 10.1016/j.ijbiomac.2023.124126. Epub 2023 Mar 20.

Abstract

Deferasirox (DFX) is an iron-chelating agent effective in treating various kinds of cancers, which inhibits iron metabolism in cancer cells. The recent study aimed to prepare an injectable thermosensitive hydrogel based on lignocellulose and agarose containing deferasirox-loaded polypyrrole nanoparticles for local drug delivery in a combined chemo-photothermal therapy by laser light irradiation. Polypyrrole nanoparticles containing DFX were made by the emulsification method and optimized. Thermosensitive hydrogels were prepared by quaternary ammonium substituted agarose and TMPO-oxidized lignocellulose at different ratios, and the optimal hydrogel was selected based on gelation time, gelation temperature, and injectability. DFX- loaded polypyrrole nanoparticles were then added to the hydrogel, and the drug release, rheology test, injectability, degradation, and swelling percent, as well as cytotoxicity, and photothermal properties, were studied on B16F10, human melanoma cells. The hydrogel with 2 % anionic lignocellulose and 0.5 % cationic agarose showed the shortest gelation time and the highest mechanical strength. It transferred from a liquid state at 4 °C into a semisolid form at 37 °C with a gelation time of 10.3 min. The nanoparticles loaded in hydrogel showed dose-dependent cytotoxicity. The cytotoxic dose of the drug was reduced by laser light irradiation.

摘要

地拉罗司(DFX)是一种铁螯合剂,可有效治疗多种癌症,它能抑制癌细胞中的铁代谢。最近的一项研究旨在制备一种基于木质纤维素和琼脂糖的可注射热敏水凝胶,其中含有负载地拉罗司的聚吡咯纳米颗粒,用于通过激光照射在联合化疗-光热疗法中进行局部药物递送。通过乳化法制备并优化了含DFX的聚吡咯纳米颗粒。采用不同比例的季铵取代琼脂糖和TMPO氧化的木质纤维素制备热敏水凝胶,并根据凝胶化时间、凝胶化温度和可注射性选择最佳水凝胶。然后将负载DFX的聚吡咯纳米颗粒添加到水凝胶中,并在B16F10人黑色素瘤细胞上研究了药物释放、流变学测试、可注射性、降解、溶胀率以及细胞毒性和光热性质。含有2%阴离子木质纤维素和0.5%阳离子琼脂糖的水凝胶显示出最短的凝胶化时间和最高的机械强度。它在4℃时从液态转变为37℃时的半固态,凝胶化时间为10.3分钟。负载在水凝胶中的纳米颗粒显示出剂量依赖性细胞毒性。激光照射降低了药物的细胞毒性剂量。

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