Focused ultrasound and microbubbles for enhanced extravasation

Area of Science:

• Biomedical Engineering
• Pharmacology
• Medical Imaging

Background:

• Blood vessel permeability is crucial for drug delivery.
• Ultrasound and microbubbles are emerging tools to modulate this permeability.
• Targeted delivery of therapeutics, like albumin-binding drugs, remains a challenge.

Purpose of the Study:

• To investigate the effect of ultrasound-mediated microbubble destruction on blood vessel permeability.
• To quantify the region of microbubble destruction and its dependence on ultrasound parameters and microbubble type.
• To evaluate the in vivo efficacy of this method for enhancing extravasation of albumin in muscle and tumor tissues.

Main Methods:

• Experiments were conducted using gel phantoms to characterize microbubble destruction zones.
• Focused ultrasound parameters (pressure, cycles) and microbubble types (lipid-shelled, polymer-shelled) were varied.
• In vivo studies utilized Evans Blue, an albumin-binding dye, to assess extravasation in muscle and MC38 tumors.
• The time window for enhanced extravasation was also investigated.

Main Results:

• Lipid-shelled microbubbles showed wider destruction areas at 2MPa compared to polymer-shelled agents (1mm radius).
• Thicker microbubble shells shifted the destruction pressure to higher values.
• In vivo, both microbubble types significantly increased albumin extravasation in muscle (6-8% injected dose/g).
• Enhanced extravasation in muscle persisted for at least an hour post-treatment.
• In MC38 tumors, ultrasound showed a trend towards enhancing extravasation (up to 3% injected dose/g), primarily in vascularized areas.

Conclusions:

• Ultrasound-mediated microbubble destruction effectively enhances blood vessel permeability for albumin.
• The method is particularly effective in muscle tissue and shows potential for tumor treatment.
• This technique could be advantageous for delivering anti-angiogenic drugs to tumors.