A new study on the skin accumulation dynamics of liposomes offers insights into how liposomes escape from blood vessels into surrounding cells and could help researchers design better drug delivery systems.
A University of Colorado Cancer Center study published today in ACS Nano describes the use of single time point and longitudinal intravital microscopy to visualize the accumulation of liposomes in skin cells, which often results in rashes or lesions and can be dose-limiting.
"We know about the dose-limiting side-effects of liposomes, but no one had looked at what happens to the liposome over time in the skin, how they get there and what happens to liposomes after injection," says Dmitri Simberg, Ph.D., investigator at the CU Cancer Center and the paper's senior author.
For the current study, working in the CU Cancer Center Advanced Light Microscopy Core, co-authors Stitch and Radu Moldovan, Ph.D., implemented intravital multiphoton in vivo microscopy that enabled the team to watch fluorescent-tagged liposomes in real-time after injection.
"Surprisingly, we saw that even liposomes with a protective coating meant to make them invisible to the immune system start exiting blood capillaries and sticking to skin cells within five minutes of injection," Simberg says. "Around three hours, we saw many skin cells loaded with liposomes and even seven days after injection, liposomes were still visible in the skin."
The current study rules out important possibilities: Liposomes are not traveling through pores in the capillaries, they are not being transported by neutrophils, they are not accumulating due to loss of protective coating, and they are not being harassed by the complement system.
Eventually, the goal is to understand the mechanisms by which liposomes leave blood vessels and are picked up by skin cells, allowing researchers to design better liposomes without skin toxicity. "At this point, we lack a mechanism for how liposomes are taken up by the skin. But we can see the dynamics, it happens very fast and it lasts surprisingly long," Simberg says.