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Inhalable stimuli-sensitive drug delivery system for controlled drug delivery to lungs

机译:可吸入的刺激敏感药物输送系统,用于控制向肺部的药物输送

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Introduction: Currently the treatment of lung cancer lacks non-invasively targetable and controlled release topical inhalation therapy. Passive targeting using iron-oxide nanoparticles and magnetic field and their ability to induce localised hyperthermia under oscillating magnetic field could potentially enable both goals in one system. This study developed temperature sensitive lipid-based drug carriers containing superparamagnetic iron-oxide nanoparticles (SPIONs) that are: inhalable, targetable and temperature-sensitive. This system exploits combined effects of pharmaceutics and hyperthermia to enhance synergistically efficacy of the cancer therapy. Materials and Methods: Fatty acids (lauric, palmitic and stearic as well as their mixtures) with melting temperature of 40 - 45oC (hyperthermia conditions) were chosen. Paclitaxel (PAX) and SPIONs were dissolved/dispersed in a melted lipid phase at different SPION/lipid ratios and solid lipid particles were produced using oil in water emulsification. The particle size, thermal properties, chemical composition were assessed using Raman spectroscopy, SEM.EDX, AFM, DSC and drug release tests. Results and Discussion: Developed particles were spherical shape, with an average diameter of 2-6 μm. Thermal and chemical analyses confirmed the presence of PAX and SPIONs inside the lipid matrix. Thermal properties of lipid microparticles, thus their ability to release the drug at specific temperature, were tuned by the formation of eutectic composition obtained by mixing different types of fatty acids. The lipid formulations were shown to have slow release profile at body temperature, but fast release at hyperthermic conditions (45°C), suggesting a potentially powerful controlled release therapy of lung cancer. Conclusion: (ⅰ) PAX and SPIONs loaded lipid microparticles of desired size and physical-chemical characteristics were fabricated using oil in water emulsification technique; (ⅱ) the lipid system was thermo-sensitive, allowing controlled release of PAX; (ⅲ) the system holds a promise as an effective drug vehicle in targeted and controlled inhalation therapy.
机译:简介:目前,肺癌的治疗缺乏非侵入性靶向和控释局部吸入疗法。使用氧化铁纳米粒子和磁场的被动靶向及其在振荡磁场下诱导局部热疗的能力可能在一个系统中同时实现两个目标。这项研究开发了基于温度敏感性脂质的药物载体,其中含有超顺磁性氧化铁纳米粒子(SPIONs):可吸入,可靶向且对温度敏感。该系统利用药剂学和热疗的联合作用来增强癌症治疗的协同功效。材料和方法:选择熔融温度为40-45oC(高温条件)的脂肪酸(月桂酸,棕榈酸和硬脂酸及其混合物)。将紫杉醇(PAX)和SPIONs以不同的SPION /脂质比例溶解/分散在熔融脂质相中,并使用水包油乳化法生产固体脂质颗粒。使用拉曼光谱,SEM.EDX,AFM,DSC和药物释放测试评估了粒径,热性能,化学成分。结果与讨论:显影后的颗粒呈球形,平均直径为2-6μm。热和化学分析证实脂质基质中存在PAX和SPIONs。通过混合不同类型的脂肪酸而形成的低共熔组合物,可以调节脂质微粒的热性能,从而调节它们在特定温度下释放药物的能力。已显示脂质制剂在体温下具有缓慢释放曲线,但在高温条件下(45°C)则具有快速释放特性,表明潜在的强大的肺癌控释治疗方法。结论:(ⅰ)采用水包油乳化技术制备了具有所需大小和理化特性的脂质微粒。 (ⅱ)脂质系统是热敏感的,可以控制PAX的释放; (ⅲ)该系统有望成为靶向和受控吸入疗法中有效的药物载体。

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