Optimization of the delivery of molecules into lymph nodes using a lymphatic drug delivery system with ultrasound
Optimization of the delivery of molecules into lymph nodes using a lymphatic drug delivery system with ultrasound
复制标题
DOI：
10.1016/j.ijpharm.2021.120324
复制
发表时间：
2021-02-09
影响因子：
5.8
通讯作者：
Kodama, Tetsuya
中科院分区：
文献类型：
--
作者：
Kato, Shigeki;Yoshiba, Shota;Kodama, Tetsuya
淋巴结（LN）转移的常规治疗（例如全身化疗）具有显着的缺点，会导致不良反应的发生。在此之前，我们已经报道了使用淋巴药物递送系统（LDDS）将药物淋巴给药到转移性LN中。然而，LDDS的先前研究尚未尝试优化有效药物递送的条件。在这里，我们研究了几个因素的影响，药物输送的效率，通过LDDS与超声（US）。首先，评价注射速率对输送效率的影响。当使用较低的注射速率时，注射到上游LN中的荧光分子被更有效地递送到下游LN中。其次，测定了分子量对药物递送效率的影响。我们发现分子量> 10，000的分子很难被递送到LN中。最后，我们评估了给药途径是否影响递送效率。我们发现，当分子被施用到靠近靶LN的上游LN中时，递送效率更高。这些发现揭示了药物的物理性质的重要性，如果它是通过LDDS管理来治疗LN转移。
Conventional treatment for lymph node (LN) metastasis such as systemic chemotherapy have notable disadvantages that lead to the development of unwanted effects. Previously, we have reported the lymphatic administration of drugs into metastatic LNs using a lymphatic drug delivery system (LDDS). However, prior studies of the LDDS have not attempted to optimize the conditions for efficient drug delivery. Here, we investigated the influence of several factors on the efficiency of drug delivery by a LDDS in conjunction with ultrasound (US). First, the effect of the injection rate on delivery efficiency was evaluated. Fluorescent molecules injected into an upstream LN were delivered more effectively into a downstream LN when a lower injection rate was used. Second, the influence of molecular weight on drug delivery efficiency was determined. We found that molecules with a molecular weight >10,000 were poorly delivered into the LN. Finally, we assessed whether the administration route affected the delivery efficiency. We found that the delivery efficiency was higher when molecules were administered into an upstream LN that was close to the target LN. These findings revealed the importance of a drug's physical properties if it is to be administered by LDDS to treat LN metastasis.