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使用气管内导管经肺部途径实现化疗颗粒向小气道肿瘤的靶向递送:一项CFPD研究。

Achieving Targeted Delivery of Chemotherapeutic Particles to Small Airway Tumors via Pulmonary Route Using Endotracheal Catheters: A CFPD Study.

作者信息

Islam Mohammad Rashedul, Feng Yu

机构信息

School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, USA.

出版信息

Pharmaceuticals (Basel). 2023 Jan 22;16(2):158. doi: 10.3390/ph16020158.

Abstract

Tracheobronchial tumors, while uncommon, are often malignant in adults. Surgical removal is the primary therapy for non-metastatic lung malignancies, but it is only possible in a small percentage of non-small-cell lung cancer patients and is limited by the number and location of tumors, as well as the patient's overall health. This study proposes an alternative treatment: administering aerosolized chemotherapeutic particles via the pulmonary route using endotracheal catheters to target lung tumors. To improve delivery efficiency to the lesion, it is essential to understand local drug deposition and particle transport dynamics. This study uses an experimentally validated computational fluid particle dynamics (CFPD) model to simulate the transport and deposition of inhaled chemotherapeutic particles in a 3-dimensional tracheobronchial tree with 10 generations (G). Based on the particle release maps, targeted drug delivery strategies are proposed to enhance particle deposition at two lung tumor sites in G10. Results indicate that controlled drug release can improve particle delivery efficiencies at both targeted regions. The use of endotracheal catheters significantly affects particle delivery efficiencies in targeted tumors. The parametric analysis shows that using smaller catheters can deliver more than 74% of particles to targeted tumor sites, depending on the location of the tumor and the catheter diameter used, compared to less than 1% using conventional particle administration methods. Furthermore, the results indicate that particle release time has a significant impact on particle deposition under the same inhalation profile. This study serves as a first step in understanding the impact of catheter diameter on localized endotracheal injection for targeting tumors in small lung airways.

摘要

气管支气管肿瘤虽不常见,但在成人中往往是恶性的。手术切除是治疗非转移性肺恶性肿瘤的主要方法,但仅适用于一小部分非小细胞肺癌患者,且受肿瘤数量、位置以及患者整体健康状况的限制。本研究提出了一种替代治疗方法:使用气管导管经肺部途径给予雾化化疗颗粒以靶向肺部肿瘤。为提高对病变部位的递送效率,了解局部药物沉积和颗粒传输动力学至关重要。本研究使用经过实验验证的计算流体颗粒动力学(CFPD)模型,来模拟吸入的化疗颗粒在具有10级分支(G)的三维气管支气管树中的传输和沉积。基于颗粒释放图,提出了靶向给药策略,以增强颗粒在第10级分支处两个肺部肿瘤部位的沉积。结果表明,控制药物释放可提高两个靶向区域的颗粒递送效率。气管导管的使用对靶向肿瘤中的颗粒递送效率有显著影响。参数分析表明,使用较小的导管可将超过74%的颗粒递送至靶向肿瘤部位,这取决于肿瘤的位置和所使用的导管直径,而传统颗粒给药方法的递送率不到1%。此外,结果表明,在相同的吸入模式下,颗粒释放时间对颗粒沉积有显著影响。本研究是了解导管直径对在小气道中靶向肿瘤的局部气管内注射影响的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9394/9965795/795f07046666/pharmaceuticals-16-00158-g001.jpg

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