Nanoscale drug-delivery capsules that release their therapeutic cargo when triggered by a temperature change could boost the efficacy and reduce the side effects of many drugs.

Researchers at RIKEN have combined lipids and peptides to create capsules with temperature-responsive controlled release behavior (Journal of the American Chemical Society, “Spontaneous formation of gating lipid domain in uniform-size peptide vesicles for controlled release”). The hybrid capsules combine the advantages of each material to enhance both capsule stability and controlled release.

Although many experimental drug-delivery capsules, or ‘vesicles’, have been developed recently, several hurdles still have to be overcome before they can be widely used in the real world, explains Motoki Ueda from the RIKEN Center for Emergent Matter Science, who co-led the study alongside Yoshihiro Ito.
“Some of the problems that still need to be solved include low stability, short circulation times in the bloodstream, controlled drug release and poor targeting of tissue,” Ueda says. “I’m convinced that soft materials can overcome these problems.”

Lipid assemblies are soft materials that have many advantages as drug-delivery vesicles, including the ability to self-assemble, biocompatibility, biodegradation, phase transitions at useful temperatures and the ability to fuse to cell membranes. But vesicles made purely from lipids are too fragile to withstand for long the physical stresses encountered when traveling through the bloodstream.

Now, Ito, Ueda and their colleagues have created high-stability, drug-delivery vesicles by combining lipids with peptides—another soft material that has the ability to self-assemble. The hybrid vesicles consisted mainly of a tough peptide material interspersed with small patches of lipid.
“The peptide-rich areas make the hybrid vesicles highly stable,” says Ueda. The hybrid vesicles are more stable than lipid vesicles, retaining their shape and structural integrity when stored for a month at 4 degrees Celsius. “On the other hand, the lipid domain underwent a phase change from gel to liquid crystal.”

Image Credit:  Alfred Pasieka


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