Crucial factors and emerging concepts in ultrasound-triggered drug delivery

Geers, Bart; Dewitte, Heleen; Smedt, Stefaan C. De; Lentacker, Ine

doi:10.1016/j.jconrel.2012.08.014

Cited by 109 publications

(69 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of small, regular contrast microbubbles such as Sonovue® or Optison® in combination with US has been shown to induce a series of biomechanical effects that may influence the extravasation, distribution, uptake and efficacy of co-administered drugs [13][14][15]. A bubble in the vascular compartment, oscillating in the sound field, will exert direct forces on the endothelial cells creating deformations.…”

Section: Discussionmentioning

confidence: 99%

“…Many of the these approaches explore the use of regular US contrast microbubbles such as Sonovue™ (Bracco Imaging S.p.A, Italy) or Optison™ (GE Healthcare AS, Norway) co-injected with various drug formulations. Insonation of the target pathology, containing microbubbles and drug in vascular compartments, leads to a variety of biomechanical effects that increase the permeability of the endothelial barrier leading to enhanced extravasation, distribution and uptake of drug molecules to target tissue [13][14][15]. Co-injection of Gemcitabine and Sonovue, with localized US insonation for enhanced drug uptake and therapeutic effect during treatment of pancreatic ductal adenocarcinoma is currently being explored in clinical trials [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

Wamel

Sontum

Healey

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12 mg/kg given i.p)., ACT induced a strong increase in therapeutic efficacy; 120 days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%. In combination with Abraxane® (12 mg paclitaxel/kg given i.v.), ACT induced a strong increase in the therapeutic efficacy; 60 days after study start 100% of the animals were in stable, remission vs. 0% for the Abraxane® only group, 120 days after study start 67% of the animals were in stable, complete remission vs. 0% for the Abraxane® only group. For the ACT + Abraxane group 100% of the animals were alive after 120 days vs. 0% for the Abraxane® only group. Proof of concept for Acoustic Cluster Therapy has been demonstrated; ACT markedly increases the therapeutic efficacy of both paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

Wamel

Sontum

Healey

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…In such a case, only a very thin stabilizing structure (e.g. phospholipid membrane or protein shell) is available for loading of microbubble formulations [15]. In addition, the circulation or lifetime of most microbubbles is typically on the order of 2-3 min, limiting the exposure time.…”

Section: Introductionmentioning

confidence: 99%

Acoustic Cluster Therapy (ACT) — pre-clinical proof of principle for local drug delivery and enhanced uptake

Wamel

Healey

Sontum

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

Proof of principle for local drug delivery with Acoustic Cluster Therapy (ACT) was demonstrated in a human prostate adenocarcinoma growing in athymic mice, using near infrared (NIR) dyes as model molecules. A dispersion of negatively charged microbubble/positively charged microdroplet clusters are injected i.v., activated within the target pathology by diagnostic ultrasound (US), undergo an ensuing liquid-to-gas phase shift and transiently deposit 20-30 µm large bubbles in the microvasculature, occluding blood flow for ~ 5-10 min. Further application of low frequency US induces biomechanical effects that increase the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g. released or co-administered drugs). Results demonstrated deposition of activated bubbles in tumor vasculature. Following ACT treatment, a significant and tumor specific increase in the uptake of a co-administered macromolecular NIR dye was shown. In addition, ACT compound loaded with a lipophilic NIR dye to the microdroplet component was shown to facilitate local release and tumor specific uptake. Whereas the mechanisms behind the observed increased and tumor specific uptake are not fully elucidated, it is demonstrated that the ACT concept can be applied as a versatile technique for targeted drug delivery.

show abstract

“…Such an over-arching principle has been the norm for the design of physically oriented drug/gene delivery paradigms [2,3]. Among various physical perforation approaches, sonoporation has been well considered as an emerging method in view of its strong potential in achieving high spatio-temporal specificity [4][5][6]. It is now established that this perforation strategy, which is founded upon acoustic cavitation principles [7,8], can readily enhance transmembranous transport [9].…”

Section: Introductionmentioning

confidence: 99%

Single-site sonoporation disrupts actin cytoskeleton organization

Chen

Leow

et al. 2014

J. R. Soc. Interface.

View full text Add to dashboard Cite

Sonoporation is based upon an ultrasound -microbubble cavitation routine that physically punctures the plasma membrane on a transient basis. During such a process, the actin cytoskeleton may be disrupted in tandem because this network of subcellular filaments is physically interconnected with the plasma membrane. Here, by performing confocal fluorescence imaging of single-site sonoporation episodes induced by ultrasound-triggered collapse of a single targeted microbubble, we directly observed immediate rupturing of filamentary actin (F-actin) at the sonoporation site (cell type: ZR-75-30; ultrasound frequency: 1 MHz; peak negative pressure: 0.45 MPa; pulse duration: 30 cycles; bubble diameter: 2-4 mm). Also, through conducting a structure tensor analysis, we observed further disassembly of the F-actin network over the next 60 min after the onset of sonoporation. The extent of F-actin disruption was found to be more substantial in cells with higher uptake of sonoporation tracer. Commensurate with this process, cytoplasmic accumulation of globular actin (G-actin) was evident in sonoporated cells, and in turn the G-actin : F-actin ratio was increased in a trend similar to druginduced (cytochalasin D) actin depolymerization. These results demonstrate that sonoporation is not solely a membrane-level phenomenon: organization of the actin cytoskeleton is concomitantly perturbed.

show abstract

Crucial factors and emerging concepts in ultrasound-triggered drug delivery

Cited by 109 publications

References 89 publications

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

Acoustic Cluster Therapy (ACT) — pre-clinical proof of principle for local drug delivery and enhanced uptake

Single-site sonoporation disrupts actin cytoskeleton organization

Contact Info

Product

Resources

About