Department of Chemical and Pharmaceutical Sciences, Kingston University London, Penrhyn Road, Kingston upon Thames, KT1 2EE, UK.
Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.
Sci Rep. 2022 Jun 10;12(1):9654. doi: 10.1038/s41598-022-13572-9.
Cryogels consisting of polyvinyl alcohol and iron (II, III) oxide magnetic nanoparticles coated with a model drug-acetaminophen, were developed as a tunable platform for thermally triggered drug release, based on shape-selective heat transfer. Two different shapes of cryogels; discs and spherical caps, were formed via adding polymer-nanoparticle-drug mixtures into 3D printed molds, followed by freeze-thawing five times. No additional chemical crosslinking agents were used for gel formation and the iron oxide nanoparticles were coated with acetaminophen using only citric acid as a hydrogen-bonding linker. The two gel shapes displayed varying levels of acetaminophen release within 42-50 °C, which are ideal temperatures for hyperthermia induced drug delivery. The amount and time of drug-release were shown to be tunable by changing the temperature of the medium and the shape of the gels, while keeping all other factors (ex. gel volume, surface area, polymer/nanoparticle concentrations and drug-loading) constant. The discs displayed higher drug release at all temperatures while being particularly effective at lower temperatures (42-46 °C), in contrast to the spherical caps, which were more effective at higher temperatures (48-50 °C). Magnetic hyperthermia-mediated thermal imaging and temperature profiling studies revealed starkly different heat transfer behavior from the two shapes of gels. The disc gels retained their structural integrity up to 51 °C, while the spherical caps were stable up to 59 °C, demonstrating shape-dependent robustness. The highly customizable physicochemical features, facile synthesis, biocompatibility and tunable drug release ability of these cryogels offer potential for their application as a low cost, safe and effective platform for hyperthermia-mediated drug delivery, for external applications such as wound care/muscle repair or internal applications such as melanoma treatment.
基于形状选择性热传递，开发了由聚乙烯醇和氧化铁磁性纳米粒子组成的冷冻凝胶，作为一种可调节的热触发药物释放平台，该冷冻凝胶涂覆有模型药物-对乙酰氨基酚。通过将聚合物-纳米粒子-药物混合物添加到 3D 打印模具中，然后进行五次冻融，形成了两种不同形状的冷冻凝胶；圆盘和球形帽。形成凝胶时未使用任何额外的化学交联剂，并且仅使用柠檬酸作为氢键连接剂将对乙酰氨基酚涂覆在氧化铁纳米粒子上。两种凝胶形状在 42-50°C 范围内显示出不同程度的对乙酰氨基酚释放，这是适用于高热诱导药物输送的理想温度。通过改变介质的温度和凝胶的形状，可以显示出药物释放的量和时间是可调的，同时保持所有其他因素（例如凝胶体积、表面积、聚合物/纳米粒子浓度和药物负载）不变。与球形帽相比，圆盘在所有温度下都显示出更高的药物释放量，而在较低温度（42-46°C）下特别有效，而球形帽在较高温度（48-50°C）下更有效。磁热疗介导的热成像和温度分布研究揭示了两种形状的凝胶具有截然不同的传热行为。圆盘凝胶在 51°C 下保持其结构完整性，而球形帽在 59°C 下保持稳定，表现出形状依赖性的坚固性。这些冷冻凝胶具有高度可定制的物理化学特性、简便的合成、生物相容性和可调节的药物释放能力，为其作为低成本、安全有效的热疗介导药物输送平台的应用提供了潜力，可用于外部应用，如伤口护理/肌肉修复，或内部应用，如黑色素瘤治疗。
