Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound

Moon, Hyungwon; Hwang, Kihwan; Nam, Kyung Mi; Kim, Yoon Seok; Ko, Min-Jung; Kim, Hyun Ryoung; Lee, Hak Jong; Kim, Mi Jeong; Kim, Tae Ho; Kang, Kyungsik; Kim, Nam Gyo; Choi, Soon Won; Kim, Chae-Yong

doi:10.1016/j.bioadv.2022.213102

Cited by 18 publications

(9 citation statements)

References 32 publications

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“…MB oscillation by cavitation leads to microstreaming and acoustic pressure, generating high shear stress on the liposomal carrier and cell membrane. Encapsulated drugs in IMP301 can be released by FUS exposure alone, but FUS-mediated MB cavitation enhances drug release and intratumoral drug penetration 14 , 16 . The mechanical stress promotes the disruption of the phospholipid shell of IMP301 and improves the dispersive transport and diffusivity of DOX to tumor cells 17 , 18 .…”

Section: Discussionmentioning

confidence: 99%

Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model

Park,

Lee,

Seo

et al. 2023

Sci Rep

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Conventional chemotherapy methods have adverse off-target effects and low therapeutic efficiencies of drug release in target tumors. In this study, we proposed a combination therapy of doxorubicin (DOX)-loaded ultrasound (US)-sensitive liposomal nanocarriers (IMP301), microbubbles (MBs) under focused US exposure using convex acoustic lens-attached US (LENS) to tumor treatment. The therapeutic effects of each treatment in a murine melanoma model were evaluated using contrast-enhanced US (CEUS) and micro-computed tomography (micro-CT) imaging, bioluminescence and confocal microscopy imaging, and liquid chromatography–mass spectroscopy (LC/MS) analysis. Tumor-bearing mice were randomly assigned to one of the following groups: (1) G1: IMP301 only (n = 9); (2) G2: IMP301 + LENS (n = 9); (3) G3: IMP301 + MB + LENS (n = 9); (4) G4: DOXIL only (n = 9); and (5) G5: IMP301 without DOXIL group as a control group (n = 4). Ten days after tumor injection, tumor-bearing mice were treated according to each treatment strategy on 10th, 12th, and 14th days from the day of tumor injection. The CEUS images of the tumors in the murine melanoma model clearly showed increased echo signal intensity from MBs as resonant US scattering. The relative tumor volume of the G2 and G3 groups on the micro-CT imaging showed inhibited tumor growth than the reference baseline of the G5 group. DOX signals on bioluminescence and confocal microscopy imaging were mainly located at the tumor sites. LC/MS showed prominently higher intratumoral DOX concentration in the G3 group than in other treated groups. Therefore, this study effectively demonstrates the feasibility of the synergistic combination of IMP301, MBs, and LENS-application for tumor-targeted treatment. Thus, this study can enable efficient tumor-targeted treatment by combining therapy such as IMP301 + MBs + LENS-application.

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Section: Discussionmentioning

confidence: 99%

Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model

Park,

Lee,

Seo

et al. 2023

Sci Rep

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“…By observing the cavitation behavior of MBs, an experiment was conducted to prevent brain damage and deliver the drug effectively, and this was confirmed in an F98 rat glioma model. Hyungwon et al studied the co-injection effect of SonoVue ® and drug-loaded ultrasound-sensitive liposomes [ 104 ]. An ultrasound-sensitive liposome is produced using the thin-film hydration method.…”

Section: Utilizing Methods Of Mbsmentioning

confidence: 99%

Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers

2023

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The blood-brain barrier (BBB) is one of the most selective endothelial barriers that protect the brain and maintains homeostasis in neural microenvironments. This barrier restricts the passage of molecules into the brain, except for gaseous or extremely small hydrophobic molecules. Thus, the BBB hinders the delivery of drugs with large molecular weights for the treatment of brain cancers. Various methods have been used to deliver drugs to the brain by circumventing the BBB; however, they have limitations such as drug diversity and low delivery efficiency. To overcome this challenge, microbubbles (MBs)-based drug delivery systems have garnered a lot of interest in recent years. MBs are widely used as contrast agents and are recently being researched as a vehicle for delivering drugs, proteins, and gene complexes. The MBs are 1–10 μm in size and consist of a gas core and an organic shell, which cause physical changes, such as bubble expansion, contraction, vibration, and collapse, in response to ultrasound. The physical changes in the MBs and the resulting energy lead to biological changes in the BBB and cause the drug to penetrate it, thus enhancing the therapeutic effect. Particularly, this review describes a state-of-the-art strategy for fabricating MB-based delivery platforms and their use with ultrasound in brain cancer therapy.

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“…In preclinical mouse models of GBM sonosensitive liposomes increased doxorubicin accumulation in the brain following ultrasound-mediated drug delivery (Fig. 2 e) [ 17 ▪ ].…”

Section: Drug Modulation Strategies Using Nanocarriersmentioning

confidence: 99%

Unveiling the enigma of the blood–brain barrier in glioblastoma: current advances from preclinical and clinical studies

Ahmed,

Canney,

Carpentier

et al. 2023

Current Opinion in Oncology

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Purpose of review Glioblastoma (GBM), the most prevalent primary brain malignancy in adults, poses significant challenges in terms of treatment. Current therapeutic strategies for GBM patients involve maximal safe resection, followed by radiotherapy with concurrent and adjuvant temozolomide. However, despite this multimodal approach for GBM, the prognosis of GBM patients remains dismal because of their inherent primary and secondary resistances to treatments. Recent findings Several molecular and cellular mechanisms, including the presence of the blood–brain barrier (BBB), contribute to these resistances. The BBB, comprising multiple layers surrounding brain vessels, acts as a barrier limiting effective drug delivery to the brain. Invasive and noninvasive tools to deliver drugs and pharmaceutical formulations locally or systemically are continuously evolving to overcome the BBB in GBM toward improving drug bioavailability in the brain and reducing systemic toxicities. Summary Preliminary studies utilizing these approaches have demonstrated promising results in terms of safety and signals of efficacy during early-phase clinical trials. However, further work through additional clinical trials is necessary to evaluate the potential clinical benefits for GBM patients.

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Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound

Cited by 18 publications

References 32 publications

Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model

Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model

Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers

Unveiling the enigma of the blood–brain barrier in glioblastoma: current advances from preclinical and clinical studies

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