Popping Droplets for Drug Delivery

Aaqib Khan – aaqib.khan@iitgn.ac.in

Chemical Engineering Department, Indian Institute of Technology Gandhinagar
Gandhinagar, Gujarat 382355
India

Sameer V. Dalvi – sameervd@iitgn.ac.in
Chemical Engineering Department,
Indian Institute of Technology Gandhinagar
Gandhinagar, Gujarat 382355
India

Popular version of 4pBAa3 – Ultrasound Responsive Multi-Layered Emulsions for Drug Delivery
Presented at the 186th ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0027523

–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–

What are popping droplets? Imagine you are making popcorn in a pot. Each little popcorn seed consists of a tiny bit of water. When you heat the seeds, the water inside them gets hot and turns into steam. This makes the seed pop and turn into a popcorn. Similarly, think of each popcorn seed as a droplet. The special liquid used to create popping droplets is called perfluoropentane (PFP), which is similar to the water inside the corn seed. PFP can boil at low temperatures and turn into a bubble, which makes it perfect for crafting these special droplets.

Vaporizable/Popping droplets hold great promise in the fields of both diagnosis and therapy. By using sound waves to vaporize PFP present in the droplets, medicine (drugs) can be delivered efficiently to specific areas in the body, such as tumors, while minimizing impacts on healthy tissues. This targeted approach has the potential to improve the safety and effectiveness of therapy, ultimately benefiting patients.

Figure 1. Vaporizable/popping droplets with perfluoropentane (PFP) in the core with successive layers of water and oil

What do we propose? Researchers have been exploring complex structures like double emulsions to load drugs onto droplets (just like filling a backpack with books), especially those that are water-soluble. Building on this, our study introduces multi-layered droplets featuring a vaporizable core (Fig.1). This design enables the incorporation of both water-soluble and insoluble drugs into separate layers within the same droplet. To better visualize this, imagine a club sandwich with layers of bread stacked on top of each other, each layer containing a different filling. Alternatively, picture an onion with multiple stacked layers that can be peeled off one by one. Similarly, multi-layered droplets comprise stacked layers, each capable of holding various substances, such as drugs or therapeutic agents.

To explore the features of the multi-layered droplets further, we carried out two separate studies. First, we estimated the peak negative pressure of the sound wave at which the PFP in the droplets vaporize. This is similar to how water boils at 100°C (212°F) under standard atmospheric pressure, but at low/negative pressure (like under a vacuum), water can boil at low temperatures. Sound waves are known to induce both positive and negative pressure changes. During instances of negative pressure, the pressure drops below the atmospheric pressure, creating a vacuum-like effect. This decrease in pressure can trigger the vaporization of the perfluoropentane (PFP) in the droplets at room temperatures.

Secondly, we loaded a water-insoluble drug, curcumin, which is an anti-inflammatory drug, in the oil layer and estimated the amount of drug loading (just like counting number of books in the backpack).

Figure 2. Relationship between Mean Grayscale (mean brightness) and soundwave pressure for droplet vaporization

Figure 2 depicts the relationship between the increase in mean grayscale (just like the increase in bright areas or brightness of a black-and-white picture) and the peak negative pressure of the sound wave. Based on our study, the peak negative pressure at which the PFP in the droplets was found to vaporize was 6.7 MPa. Furthermore, the loading for curcumin was estimated to be 0.87 ± 0.1 milligrams (mg), which indicates a higher drug loading capacity in multi-layered droplets.

These studies are essential because they help us determine two critical things. The first one allows us to figure out the exact sound wave pressure needed to make the droplets pop. This is useful for the controlled release of drugs in targeted areas. The second study tells us how much drug these droplets can hold, which is helpful in designing drug delivery systems.

Together, these studies enhance our understanding of multi-layered droplets and pave the way for a new targeted therapy, where popping droplets serve as vehicles for delivering drugs or therapeutic agents to specific locations upon activation by sound waves.