Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation
Summary & key facts
The researchers built tiny drug carriers called liposomes that release medicine only when hit by short bursts of low-intensity ultrasound. They changed the liquid inside the liposomes using an inactive ingredient that is already considered safe in medicines. In lab tests the liposomes could carry and release four different drugs on demand. In live animal experiments, the same idea let them change nerve activity without surgery, by releasing drugs at the exact spot the ultrasound was aimed. The team says this design uses common pharmaceutical materials and methods, which could make it easier to develop for human use, but the work so far is in lab and animal tests, not yet in people.
- Liposomes are tiny, medicine-carrying bubbles made from fats. The team tuned how they respond to sound by changing the liquid inside them with an inactive ingredient that is regarded as safe.
- In laboratory tests, these modified liposomes could be loaded with and release four different drugs when exposed to short, low-intensity pulses of ultrasound.
- The ultrasound used is noninvasive sound energy that can be focused to a small spot. When applied, it triggered drug release only where the sound was aimed.
- The researchers used the drug release to change nerve activity in live animals. They showed noninvasive drug-mediated neuromodulation of both the central nervous system (the brain and spinal cord) and peripheral nerves.
- Because the liposomes were made with common, validated pharmaceutical ingredients and production steps, the authors say this approach could have higher potential for clinical translation than systems that use unvalidated materials.
- All results reported so far come from lab experiments and animal studies. The method has not yet been tested for safety or effectiveness in people.
Abstract
Stimulus-responsive drug delivery nanotechnologies promise noninvasive activation of the right drug at the right place at the right time. However, these systems often incorporate non-validated pharmaceutical excipients and other features that limit their clinical translation. Here we engineer the responsiveness of liposomes to a pulsed, low-intensity ultrasound activating stimulus by incorporating a generally regarded as safe excipient that alters the acoustic properties of the liposome core medium. We show that this approach permits loading and ultrasound-induced release of four drugs in vitro. We then leverage this performance to enable drug-mediated noninvasive neuromodulation of each of the central and the peripheral nervous system in vivo. These acoustically activatable liposomes formulated with common and validated pharmaceutical excipients and production processes provide a versatile system for stimulus-responsive site-targeted drug delivery and noninvasive neuromodulation, with high clinical translation potential.