Technology
BUS-DDS (Bubble Ultrasound-mediated Drug Delivery System)
Unmet Medical Needs
In cancer and central nervous system (CNS) diseases, drug delivery is severely limited by biological barriers.
In solid tumors, the tumor vascular barrier restricts drug penetration, while in the brain, the blood–brain barrier (BBB) prevents most therapeutics from reaching neural tissue.
Overcoming these barriers is essential to improving therapeutic outcomes.
Tumor Vessels Barriers
The irregular vascular structure and rich stromal environment limit drug penetration into cancer tissue.
Blood Brain Barrier(BBB)
Tight endothelial junctions in the brain prevent effective drug delivery.
Technology Overview
BUS-DDS (Bubble-mediated Ultrasound Drug Delivery System) is Wellthera’s proprietary drug delivery platform that transiently and reversibly modulates biological barriers to enhance drug delivery to target tissues.
By combining therapeutic microbubbles with low-intensity, non-invasive ultrasound, BUS-DDS enables localized and targeted delivery to otherwise hard-to-reach tissues, including solid tumors and the central nervous system.
Theranostic Bubble (TB)
Theranostic Bubbles (TBs) are therapeutic microbubbles developed at Teikyo University and advanced by Wellthera, enabling safe and transient modulation of biological barriers under low-intensity ultrasound. [1]
Treatment Process
In BUS-DDS–based treatment, Theranostic Bubbles (TBs) are administered intravenously, and the target tissue is visualized in real time using ultrasound imaging.
Low-intensity ultrasound is then applied locally, followed by standard drug administration, enabling non-invasive and localized enhancement of drug delivery.
BUS-DDS can be integrated into existing treatment protocols without major changes to drug formulation or administration routes.
Therapeutic Applications for BUS-DDS
BUS-DDS is being developed by Teikyo University and Wellthera for oncology and CNS applications, including BBB opening, and is applicable across a wide range of modalities regardless of molecular size.
Oncology
BUS-DDS enhances intratumoral delivery of anticancer agents limited by tumor vascular barriers, providing a platform for improved therapeutic efficacy in solid tumors.
Enhanced Drug Delivery to Tumor Tissues
In colorectal tumor-bearing mice, the concentration of Doxil® in tumor tissues increased approximately 5-fold 6 hours after +TB administration when combined with ultrasound irradiation (p<0.01).
Enhanced Anti-Tumor Efficacy
In endometrial tumor-bearing mice, cisplatin + TB + ultrasound significantly suppressed tumor volume growth compared to cisplatin + TB alone (p<0.05) [2]
Central Nervous System Disorders (BBB Opening)
BUS-DDS enables delivery of therapeutic agents across the BBB, supporting CNS drug development across a wide range of modalities, from small molecules to nucleic acids and antibodies.
Enhanced Penetration into Brain Tissues
In mice injected intravenously with Evans Blue dye and TB, ultrasound irradiation applied to the right hemisphere led to over a 3-fold increase in dye accumulation (p<0.01). [3]
Increased Gene Expression in Brain
In mice IV administered mRNA-LNP encoding luciferase and TB, ultrasound irradiation applied to the right hemisphere resulted in over a 10-fold increase in luciferase expression (p<0.01). [4]
Pipeline
Pancreatic cancer is our lead indication, with non-clinical studies progressing toward clinical trials.
BUS-DDS is also being explored for other solid tumors and a range of drug modalities, including small molecules, antibodies, nucleic acids, and liposomes.
In the mid- to long term, we aim to expand into CNS disorders using BBB-opening technology.
[1] Maruyama, Innovative DDS technology using microbubbles and ultrasound (in Japanese), Phama Tech Japan, 41, 1372-1379 , 2025
[2] Yamaguchi et.al, Enhanced antitumor activity of combined lipid bubble ultrasound and anticancer drugs in gynecological cervical cancers. Cancer Science 112, 2493–2503, 2021
[3] Unga et.al, Effects of Encapsulated Gas on Stability of Lipid-based Microbubbles and Ultrasound-triggered Drug Delivery. J. Control. Release 311-312, 65-73, 2019
[4] Ogawa et.al, Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain. J. Controlled Release 348, 34-41, 2022