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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递送系统,用于控制药物递送给肺部

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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:介绍:目前肺癌的治疗缺乏无侵入性的局部靶向和控释局部吸入疗法。使用氧化铁纳米颗粒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会在一个系统中实现两个目标。该研究开发出含有超顺磁性氧化铁纳米颗粒(栓塞)的温度敏感的基于脂质的药物载体,即:可吸入,可用于温度和温度敏感。该系统利用药物和热疗的组合效应来增强癌症治疗的协同效果。选择材料和方法:选择脂肪酸(月桂,棕榈和硬脂酸和它们的混合物),熔化温度为40-45℃(热疗条件)。紫杉醇(Pax)和散射在不同的Spion /脂质比下溶解/分散在熔化的脂质相中,并在水乳化中使用油制备固体脂质颗粒。使用拉曼光谱,SEM.EDX,AFM,DSC和药物释放试验评估粒度,热性质,化学成分。结果与讨论:开发颗粒是球形,平均直径为2-6μm。热和化学分析证实了脂质基质内部存在的pax和散热。通过形成通过混合不同类型的脂肪酸获得的共晶组合物来调整脂质微粒的热性能,从而通过形成共晶组合物进行调节。脂质制剂显示在体温下具有缓慢的释放曲线,但在高温条件下快速释放(45℃),表明肺癌的可能强大的控释治疗。结论:(Ⅰ)使用水乳化技术用油制造了PAX和散热脂质微粒的所需尺寸和物理化学特性; (Ⅱ)脂质体系是热敏的,允许受控释放pax; (Ⅲ)该系统在有效的药物载体中持有靶向和控制的吸入治疗。

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