An in vitro feasibility study of controlled drug release from encapsulated nanometer liposomes using high intensity focused ultrasound

AbstractAn approach to improve chemotherapy, while minimizing side effects, is a local drug release close to the tumorous tissue. For this purpose, the active drug component is often bound to nanoparticles employed as drug carriers. In the present study, we investigate sonosensitive, biocompatible poly-(L)-lactic acid (PLA) nanoparticles, which shall be used as drug carriers. For drug release, High Intensity Focused Ultrasound (HIFU) will be employed to introduce inertial cavitation, which separates the active drug component from the drug carrier. The cavitation effect generates an acoustic noise signal, which characterizes the cavitation activity and is expected to serve simultaneously as an indicator for the release of the active drug component. Depending on the ultrasound frequency, different acoustic levels of the inertial cavitation activity were measured. Investigations using a setup for passive cavitation detection (PCD) deliver quantitative results regarding the frequency dependence of the cavitation activity level of nanoparticles and reference media.

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A Doxorubicin-Glucuronide Prodrug Released from Nanogels Activated by High-Intensity Focused Ultrasound Liberated β-Glucuronidase

Pharmaceutics ◽

10.3390/pharmaceutics12060536 ◽

2020 ◽

Vol 12 (6) ◽

pp. 536

Author(s):

Helena C. Besse ◽

Yinan Chen ◽

Hans W. Scheeren ◽

Josbert M. Metselaar ◽

Twan Lammers ◽

...

Keyword(s):

Molecular Weight ◽

Anticancer Drugs ◽

High Intensity ◽

Focused Ultrasound ◽

Anticancer Therapy ◽

High Intensity Focused Ultrasound ◽

Low Molecular Weight ◽

Chemotherapeutic Drug ◽

The Poor

The poor pharmacokinetics and selectivity of low-molecular-weight anticancer drugs contribute to the relatively low effectiveness of chemotherapy treatments. To improve the pharmacokinetics and selectivity of these treatments, the combination of a doxorubicin-glucuronide prodrug (DOX-propGA3) nanogel formulation and the liberation of endogenous β-glucuronidase from cells exposed to high-intensity focused ultrasound (HIFU) were investigated in vitro. First, a DOX-propGA3-polymer was synthesized. Subsequently, DOX-propGA3-nanogels were formed from this polymer dissolved in water using inverse mini-emulsion photopolymerization. In the presence of bovine β-glucuronidase, the DOX-propGA3 in the nanogels was quantitatively converted into the chemotherapeutic drug doxorubicin. Exposure of cells to HIFU efficiently induced liberation of endogenous β-glucuronidase, which in turn converted the prodrug released from the DOX-propGA3-nanogels into doxorubicin. β-glucuronidase liberated from cells exposed to HIFU increased the cytotoxicity of DOX-propGA3-nanogels to a similar extend as bovine β-glucuronidase, whereas in the absence of either bovine β-glucuronidase or β-glucuronidase liberated from cells exposed to HIFU, the DOX-propGA3-nanogels hardly showed cytotoxicity. Overall, DOX-propGA3-nanogels systems might help to further improve the outcome of HIFU-related anticancer therapy.

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TH-C-204B-06: MR Guided High-Intensity Focused Ultrasound for Cancer Therapy: A Feasibility Study Using an Animal Model

Medical Physics ◽

10.1118/1.3469499 ◽

2010 ◽

Vol 37 (6Part13) ◽

pp. 3456-3456

Author(s):

C Ma ◽

Z Mu ◽

L Chen

Keyword(s):

Animal Model ◽

Cancer Therapy ◽

Feasibility Study ◽

High Intensity ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound

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Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound

Scientific Reports ◽

10.1038/s41598-019-52012-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Heikki J. Nieminen ◽

Eetu Lampsijärvi ◽

Gonçalo Barreto ◽

Mikko A. J. Finnilä ◽

Ari Salmi ◽

...

Keyword(s):

Methylene Blue ◽

Articular Cartilage ◽

High Intensity ◽

Focused Ultrasound ◽

Pulse Repetition Frequency ◽

High Intensity Focused Ultrasound ◽

Positive Pressure ◽

Mechanical Index ◽

Localized Delivery

Abstract Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.

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