4.7 Article

Optimization of the delivery of molecules into lymph nodes using a lymphatic drug delivery system with ultrasound

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 597, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120324

Keywords

Lymph node metastasis; Ultrasound; Drug delivery; Chemotherapy; Lymphatic vessel; Acoustic liposome

Funding

  1. JSPS KAKENHI [17K13039, 19K16622, 17K20077, 17H00865, 19K22941, 20H00655]
  2. Grants-in-Aid for Scientific Research [20H00655, 17K20077, 17H00865, 17K13039, 19K16622, 19K22941] Funding Source: KAKEN

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This study investigated the factors influencing drug delivery efficiency using LDDS with ultrasound, including injection rate, molecular weight, and administration route. The results showed that lower injection rate, smaller molecular weight, and administration into an upstream LN close to the target LN could improve delivery efficiency.
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.

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