Ultrasound-responsive Liposome Development Service

At the vanguard of pharmaceutical innovation, Creative Biolabs has developed a comprehensive suite of stimuli-responsive liposomal solutions, including ultrasound-responsive liposome, designed to address the diverse and sophisticated needs of smart drug delivery. These advanced systems are engineered to harness the precision of ultrasound to trigger the release of encapsulated drugs, offering a new dimension in targeted drug administration.

Background

Ultrasound (US), a high-frequency mechanical wave with frequencies exceeding 20 kHz, is characterized by its non-invasiveness, spatial accuracy, and the ability to be used repeatedly without leaving any radiation residue. Compared to light and other stimulus-responsive techniques, ultrasound demonstrates enhanced controllability, superior tissue penetration, minimal harm to surrounding healthy tissues, and the unique ability to combine diagnostic and therapeutic procedures.

What is Ultrasound-responsive Liposome?

Ultrasound-sensitive liposome, also known as ultrasound-triggered liposome, penetrate tissues under varying intensities of applied ultrasound and undergo processes of contraction, oscillation, expansion, and disruption, leading to responsive drug release at the target site. This mechanism minimizes adverse systemic side effects on healthy tissues, aiding in the achievement of therapeutic goals. By modulating ultrasound parameters such as frequency and intensity, targeted and quantified drug release in the area of interest can be achieved. High-Intensity focused ultrasound is frequently used as an external stimulus for ultrasound-responsive liposome to trigger drug release.

For an ideal ultrasound-responsive liposome, two critical conditions must be met:

• The drug must be stably encapsulated within the liposome prior to ultrasound exposure.
• Upon ultrasound exposure, a substantial release of the drug from the liposome should occur.

Mechanisms of Drug Delivery in Ultrasound-responsive Liposome

Ultrasound-responsive liposome harness thermal and mechanical effects to rupture liposome, release drugs, and inflict mechanical damage or increase temperature in target tissues or cells. Ultrasound can also elevate intracellular reactive oxygen species (ROS), enhancing the fluidity of phospholipids and thereby promoting drug uptake.

• Thermal Effects: As ultrasound propagates, it induces proton vibrations, with a portion of the frictional energy converting into heat, which raises tissues or cells temperature, enhancing permeability and facilitating liposome uptake. Ultrasound-induced high temperatures can eradicate cells and degrade proteins and other structures without significantly harming surrounding healthy tissues.
• Mechanical Effects: High-frequency vibrations from ultrasound alter the permeability of liposomes, accelerating drug release. Cavitation: Cavitation involves pressure fluctuations that create and cause cavities to grow, oscillate, and collapse. The implosive forces and microjets from collapsing cavitation bubbles, also known as sonoporation, can create pores in tumor vasculature and cell membrane, enhancing the extravasation of liposomes and subsequent delivery of payloads to the tumor site. This allows non-permeable compounds to enter cells through the pores created in the membrane.
  Acoustic Radiation Forces: It refers to the unidirectional force exerted by ultrasound waves on absorbent or reflective bodies in their path. This force, or the acoustic streaming it generates, can displace liposomes in the blood and direct them towards targeted tissues, leading to reversible structural alterations.
• Sonochemical Effects: The high temperatures induced by cavitation can lead to the production of reactive radicals from sonosensitizers. These radicals can interact with other molecules in the aqueous environment, generating reactive oxygen species (ROS). These include hydroxyl free radicals and singlet molecular oxygen, which induce apoptosis in tumor cells. The generation of ROS depends on the ultrasound intensity, the sonosensitizer used, and the strength and frequency of cavitation events.

Based on these mechanisms, ultrasound can achieve efficient controlled drug release, enhance the permeability of diseased tissues and cell membranes, and promote cellular uptake of drugs.

Fig.1 Ultrasound-induced mechanical effects.¹

Impact of Ultrasound Parameters on Drug Release

Ultrasound Frequency: The attenuation and absorption of ultrasound waves in a medium are closely related to frequency. At higher frequencies, ultrasound energy is more readily attenuated and absorbed, reducing penetration into deeper tissues. Therefore, at high frequencies, thermal effects play a predominant role in energy transfer. In contrast, cavitation is more significant at lower frequencies. Lowering the ultrasound frequency enhances penetration depth, cavitation likelihood, and heating.

Ultrasound Intensity: Ultrasound intensity is defined as the power of the ultrasound beam divided by the surface area over which it propagates, and it is directly related to medium density, acoustic pressure, and the speed of ultrasound propagation in the medium. Increasing the intensity of the ultrasound allows for the control of energy delivery to the target site.

Advantages of Ultrasound-responsive Liposome by Creative Biolabs

• Cost-Effective and User-Friendly: Our ultrasound-responsive liposome offers a low-cost solution that is simple to operate, ensuring safety and non-invasiveness in drug delivery procedures.
• Repeatable Drug Administration: With the ability to trigger drug release upon repeated ultrasound application, our technology reduces the dosage and frequency of medication administration, providing a more efficient treatment approach.
• Broad Application Spectrum: Our liposomes are versatile, with applications spanning various therapeutic areas including tumors, ischemic myocardium, neurodegenerative diseases, skeletal muscle diseases, and the disruption of the blood–brain barrier.
• Innovation and Research: At Creative Biolabs, we excel in ultrasound-responsive liposome innovation, consistently advancing the frontiers and establishing new benchmarks in this cutting-edge field.

Creative Biolabs' ultrasound-responsive liposome exemplifies our commitment to leading-edge technology in drug delivery. To delve into the potential of our advanced solutions and integrate them into your treatment protocols, we invite you to contact us.

For Research Use Only. Not For Clinical Use