Researchers have developed a technology that creates nanoscale pouches with a compartment within a compartment, like Russian nesting dolls. The new technology can deliver two drugs simultaneously or at different times.
Scientists and researchers are working hard to develop new and better drug delivery methods that increase effectiveness and reduce potential side effects. Nanoscale liposomes, tiny artificially created sacs consisting of an aqueous solution surrounded by a bilayered membrane of lipid (fat) molecules, are widely used as drug carriers because they are versatile, biodegradable, and less likely to cause allergic reactions.
However, current methods of liposome synthesis limit the ability to produce complex structures and typically produce liposomes with a single drug-carrying compartment. Now, researchers from Imperial College London (ICL) have developed a technology that creates liposomes with compartments within compartments, allowing much greater control over drug delivery.
“Like Russian dolls, our technology allows us to create particle-within-a-particle structures, providing the ability to control all the properties of each particle, including the drug or vaccine encapsulated inside it,” said Dr. Yuval Elani, from ICL's Department of Chemical Engineering and corresponding author of the study. “With further research to examine how these nanoparticles interact with living organisms, this development holds significant potential to revolutionize both therapeutics, such as chemotherapies and vaccines.”
Synthesizing the 'Russian doll' architecture of one compartment inside another, which the researchers call 'concentrosomes', involved layering outer lipid membranes on top of inner membranes. They did this by combining microfluidics, manipulating small amounts of liquid using micron-scale channels, and using 'click chemistry', a simple technique that produces new compounds in high yields using readily available starting materials.
The resulting concentrosomes are microscopic: about 200 nanometers across. To give some context, a human hair is about 80,000 to 100,000 nm wide; most proteins are about 10 nm wide, whereas a typical virus is about 100 nm wide.
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“Just as the structural complexity of animal cells enables them to have complex functions, compartmentalized nanoparticles can be tuned to exhibit more advanced properties,” Elani said.
The researchers were able to control the composition of each lipid bilayer to make the concentrateome user-defined. For example, they developed a system where one layer is temperature-sensitive, meaning it is thermoreactive, and the other is not, so that the contents are only released when a certain temperature is reached.
With further experiments, they showed that the inner and outer concentrisome membranes could hold different drug cargoes and release each at different stages. Exposing the concentrisome to a low temperature caused the outer membrane to release its cargo; successive exposures to high temperatures caused the inner membrane to release. Even more impressive was the researchers’ ability to engineer the concentrisomes to synthesize new biochemicals within themselves, again triggered by an increase in temperature.
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The ability to give two drugs simultaneously or at different time points has the potential to revolutionize combination therapies, or the use of multiple drugs to treat a single disease.
The drug delivery technology is currently at the proof-of-concept stage and has not been tested in vivo. Future research is required to increase the architectural complexity of concentrosomes and to use different payloads such as genetic material before these promising preliminary findings can be translated into practical applications.
The study was published in the journal Nature Chemistry.
Source: ICL via EurekAlert!