光热响应型控释微球的可控制备及其性能

doi:10.16085/j.issn.1000-6613.2023-0374

摘要/Abstract

摘要：

单一的光热治疗（PTT）效果有限，往往不能彻底治愈肿瘤。随着材料科学与生物医学的融合，多功能药物载体材料得到了很好的开发利用，有助于将PTT与其他治疗方法联合使用，为协同增强抗肿瘤疗效提供了有效的策略。本研究以载有吲哚菁绿（ICG）的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒子为光热剂，以聚乙烯醇（PVA）/海藻酸钠（SA）为载体基材，采用微流控技术可控制备了一种新型光热响应型控释微球（PLGA-ICG@PVA/SA）。系统研究了微球的形貌尺寸可控性、光热转化性能、机械性能和生物相容性，并以盐酸阿霉素（DOX）为模型药物，探讨了该微球载体对DOX的负载能力和光热响应性控释能力。结果表明，所制备的PLGA-ICG@PVA/SA微球具有良好的单分散性，表现出优异的光热转换效应，0.5W/cm²近红外光照射15min的温度增量为18.5℃且稳定性良好；微球亦具有良好的可压缩性和弹性性能，其杨氏模量为317.0kPa。在模拟生理环境中，微球中DOX药物的释放行为符合一级释放动力学模型并具有明显的光热刺激响应性。该微球材料在药物控释及肿瘤的光热/化疗联合治疗等领域具有广泛的应用前景。

关键词: 微流体学, 光热治疗, 复合微球, 吲哚菁绿, 纳米粒子, 药物释放, 弹性

Abstract:

Single photothermal therapy (PTT) has limited effects and often cannot cure tumors completely. With the integration of material science and biomedicine, multifunctional drug carrier materials have been well developed and utilized, which is conducive to the combined use of PTT with other therapeutic methods, providing an effective strategy for synergistically enhancing antitumor efficacy. In this study, a novel kind of photothermal responsive controlled-release microspheres (PLGA-ICG@PVA/SA) was controllably fabricated by microfluidic technology using poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with indocyanine green (ICG) as the photothermal agent and poly(vinyl alcohol) (PVA)/sodium alginate (SA) as the carrier substrate. The morphology and size controllability, photothermal conversion performance, mechanical properties and biocompatibility of microspheres were systematically investigated. Taking doxorubicin hydrochloride (DOX) as a model drug, the loading capacity and photothermal responsive controlled-release capacity of the microspheres were studied. The results showed that the prepared PLGA-ICG@PVA/SA microspheres had good monodispersity and excellent photothermal conversion effect. The temperature increment was 18.5℃ under 0.5W/cm² NIR light irradiation for 15min, and the stability was good. The microspheres also had good compressibility and elasticity with a young's modulus of 317.0kPa. In the simulated physiological environment, the release behavior of DOX drug from microspheres conformed to the first-order release kinetic model and exhibited an obvious photothermal response. This microsphere material had broad application prospects in the fields of drug controlled-release and photothermal/chemotherapeutic combination therapy of tumors.

Key words: microfluidics, photothermal therapy, composite microspheres, indocyanine green, nanoparticles, drug release, elasticity

中图分类号:

TQ469

杨嘉琪, 巨晓洁, 谢锐, 汪伟, 刘壮, 潘大伟, 褚良银. 光热响应型控释微球的可控制备及其性能[J]. 化工进展, 2024, 43(3): 1474-1483.

YANG Jiaqi, JU Xiaojie, XIE Rui, WANG Wei, LIU Zhuang, PAN Dawei, CHU Liangyin. Controllable preparation and properties of photothermal-responsive controlled-release microspheres[J]. Chemical Industry and Engineering Progress, 2024, 43(3): 1474-1483.

图/表 11

图1 PLGA-ICG@PVA/SA微球的制备及其光热响应性药物释放示意图

图2 PLGA-ICG纳米粒子的SEM图、粒径分布与zeta电位

表1 微球尺寸与制备条件参数表

序号

内外相流速比

液滴直径

/μm

微球直径

/μm

微球直径CV值

收缩比

图3 不同尺寸PLGA-ICG@PVA/SA液滴和微球的光学照片

图4 不同功率密度NIR照射下微球混悬液的光热转化规律

图5 0.5W/cm2的NIR照射PLGA-ICG@PVA/SA微球混悬液5个开/关循环的光热曲线

图6 PLGA-ICG/DOX@PVA/SA微球的载药性能

图7 PLGA-ICG/DOX@PVA/SA微球在PBS溶液中的药物累积释放量和释药动力学

图8 PLGA-ICG@PVA/SA微球和PLGA-ICG/DOX@PVA/SA微球的弹性性能

图9 不同浓度PLGA-ICG@PVA/SA微球溶血率

图10 不同浓度PLGA-ICG@PVA/SA微球与L929细胞分别共培养24h、48h和72h后的细胞毒性

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