Xi Jinxiang, Yuan Jiayao Eddie, Si Xiuhua April, Hasbany James
School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.
Department of Mechanical Engineering, California Baptist University, Riverside, CA, USA.
Int J Nanomedicine. 2015 Jul 30;10:4847-61. doi: 10.2147/IJN.S87382. eCollection 2015.
Despite the prevalence of rhinosinusitis that affects 10%-15% of the population, current inhalation therapy shows limited efficacy. Standard devices deliver <5% of the drugs to the sinuses due to the complexity of nose structure, secluded location of the sinus, poor ventilation, and lack of control of particle motions inside the nasal cavity.
An electric-guided delivery system was developed to guide charged particles to the ostiomeatal complex (OMC). Its performance was numerically assessed in an MRI-based nose-sinus model. Key design variables related to the delivery device, drug particles, and patient breathing were determined using sensitivity analysis. A two-stage optimization of design variables was conducted to obtain the best performance of the delivery system using the Nelder-Mead algorithm.
The OMC delivery system exhibited high sensitivity to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric guidance and point drug release, the new delivery system eliminated particle deposition in the nasal valve and turbinate regions and significantly enhanced the OMC doses. An OMC delivery efficiency of 72.4% was obtained with the optimized design, which is one order of magnitude higher than the standard nasal devices. Moreover, optimization is imperative to achieve a sound delivery protocol because of the large number of design variables. The OMC dose increased from 45.0% in the baseline model to 72.4% in the optimized system. The optimization framework developed in this study can be easily adapted for the delivery of drugs to other sites in the nose such as the ethmoid sinus and olfactory region.
尽管鼻窦炎患病率高达10%-15%，但目前的吸入疗法疗效有限。由于鼻腔结构复杂、鼻窦位置隐蔽、通气不良以及鼻腔内颗粒运动缺乏控制，标准装置仅能将<5%的药物输送至鼻窦。
开发了一种电引导输送系统，以引导带电粒子至窦口鼻道复合体（OMC）。在基于磁共振成像（MRI）的鼻窦模型中对其性能进行了数值评估。通过敏感性分析确定了与输送装置、药物颗粒和患者呼吸相关的关键设计变量。使用Nelder-Mead算法对设计变量进行两阶段优化，以获得输送系统的最佳性能。
OMC输送系统对施加的电场和粒子携带的静电荷表现出高度敏感性。通过电引导和定点药物释放的结合，新的输送系统消除了鼻瓣和鼻甲区域的颗粒沉积，并显著提高了OMC的药物剂量。优化设计后OMC输送效率达到72.4%，比标准鼻腔装置高一个数量级。此外，由于设计变量众多，优化对于实现良好的输送方案至关重要。OMC剂量从基线模型中的45.0%增加到优化系统中的72.4%。本研究中开发的优化框架可轻松适用于将药物输送至鼻腔的其他部位，如筛窦和嗅觉区域。
