Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes

Olsman, Marieke; Sereti, Viktoria; Andreassen, Kristine; Snipstad, Sofie; Wamel, Annemieke van; Eliasen, Rasmus; Berg, Sigrid; Urquhart, Andrew J.; Andresen, Thomas Lars; Davies, Catharina de Lange

doi:10.1016/j.jconrel.2020.06.024

Cited by 40 publications

(15 citation statements)

References 50 publications

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“…Similarly, in a study using liposomes in the PC3 model, our group has previously observed increased penetration in a distance up to 60 µm from blood vessels. [ 53 ] Similar penetration distance was observed here and shows that the increased penetration is not merely an effect of increased NP accumulation, but rather that the NPs are pushed deeper into the tissue showing that sonopermeation has consequences also at a distance from the blood vessel wall. In OHS tumors, increased extravasation distance was not observed, both treated and untreated tumors showed comparable NP extravasation as the PC3 group.…”

Section: Discussionsupporting

confidence: 78%

Sonopermeation with Nanoparticle‐Stabilized Microbubbles Reduces Solid Stress and Improves Nanomedicine Delivery to Tumors

Sulheim

Hanson

Snipstad

et al. 2021

Advanced Therapeutics

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Drug delivery to tumors is challenging due to biological barriers obstructing effective delivery. Sonopermeation with ultrasound and microbubbles has been shown to improve therapeutic effect of many classes of drugs, but the underlying mechanism is not fully understood. In this study, two subcutaneous xenograft tumor models, that differed substantially in blood vessel density and stiffness, is treated with poly(alkyl cyanoacrylate) nanoparticles and nanoparticle‐stabilized microbubbles combined with ultrasound. Improved nanoparticle accumulation and extracellular matrix (ECM) penetration is found. The stiffness and solid stress in the tumors are measured and it is discovered that sonopermeation can reduce the solid stress in both models, with the highest effect in the stiffest tumor model. This suggests that sonopermeation affects not only the blood vessel wall which has been described previously, but also the ECM to reduce solid stress and increase diffusion and transport of nanomedicines.

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Section: Discussionsupporting

confidence: 78%

Sonopermeation with Nanoparticle‐Stabilized Microbubbles Reduces Solid Stress and Improves Nanomedicine Delivery to Tumors

Sulheim

Hanson

Snipstad

et al. 2021

Advanced Therapeutics

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“…Bush et al [ 33 ] found no difference between a one-min and a five-min US trigger for acoustic cluster therapy. Olsman et al [ 34 ] also found no difference with increasing US intensity. In addition, Bourn et al [ 35 ] found no difference with an increasing number of triggers (in vitro spheroid under fluid flow).…”

Section: Discussionmentioning

confidence: 95%

A Single Short ‘Tone Burst’ Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles

et al. 2022

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Advanced drug delivery systems, such as ultrasound-mediated drug delivery, show great promise for increasing the therapeutic index. Improvements in delivery by altering the ultrasound parameters have been studied heavily in vitro but relatively little in vivo. Here, the same therapeutic microbubble and tumour type are used to determine whether altering ultrasound parameters can improve drug delivery. Liposomes were loaded with SN38 and attached via avidin: biotin linkages to microbubbles. The whole structure was targeted to the tumour vasculature by the addition of anti-vascular endothelial growth factor receptor 2 antibodies. Tumour drug delivery and metabolism were quantified in SW480 xenografts after application of an ultrasound trigger to the tumour region. Increasing the trigger duration from 5 s to 2 min or increasing the number of 5 s triggers did not improve drug delivery, nor did changing to a chirp trigger designed to stimulate a greater proportion of the microbubble population, although this did show that the short tone trigger resulted in greater release of free SN38. Examination of ultrasound triggers in vivo to improve drug delivery is justified as there are multiple mechanisms at play that may not allow direct translation from in vitro findings. In this setting, a short tone burst gives the best ultrasound parameters for tumoural drug delivery.

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“…The increase in systemic absorption of pirarubicin by US-triggered microbubble cavitation was not prominent in this preliminary study. Previous studies showed that the penetration distance of nanoscale agents by UStriggered microbubble cavitation in in vivo models was up to 80 µm depending on the acoustic intensity and size of agents (Theek et al, 2016;Yemane et al, 2019;Olsman et al, 2020). Therefore, it may be possible that US-triggered microbubble cavitation increases the extravasation of pirarubicin into the bladder wall, and thereafter pirarubicin rapidly diffuses into epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study

et al. 2022

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Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure −1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.

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Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes

Cited by 40 publications

References 50 publications

Sonopermeation with Nanoparticle‐Stabilized Microbubbles Reduces Solid Stress and Improves Nanomedicine Delivery to Tumors

Sonopermeation with Nanoparticle‐Stabilized Microbubbles Reduces Solid Stress and Improves Nanomedicine Delivery to Tumors

A Single Short ‘Tone Burst’ Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles

Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study

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