Bortezomib treatment using liposome nanocarriers leads to decreased cell viability and greater apoptosis in vitro, compared with treatment with free bortezomib, according to a study in the Journal of Pharmaceutical Sciences and Pharmacology.
Liposomes are lipid sacs with a watery compartment, which can be used to encapsulate and deliver a therapeutic cargo. The delivery method has been found to have improved efficacy with lesser side effects.
Dennis Barten/Wikimedia Commons/CC-ASA 3.0
Ceramide liposomes are an attractive drug-delivery vehicle, the researchers said, because of their cell-permeability and because they’ve been found, on their own, to mediate apoptosis. Researchers said they believed this was the first time results have been reported on combining ceramide liposomes with an anticancer drug such as bortezomib. Cationic liposomes were picked because they’re known to destabilize cell membranes, helping with intracellular delivery of the drug.
Free bortezomib and bortezomib loaded into liposomes were tested for efficacy on mouse preosteoclast calvaria MC3T3 cells, mouse macrophage-like RAW 264.7 cells, and human osteosarcoma U2OS cells.
On the RAW 264.7 cells, researchers found a significant difference in cell viability between free bortezomib and ceramide liposomes after 24 hours (P less than .01) and 48 hours (P less than .05) and between free bortezomib and cationic liposomes at 24 hours (P less than .01). They also reported a significant difference with cationic liposomes on MC3T3 cells and U2OS cells at 48 hours (both P less than .01).
One nanomolar (nM) of ceramide-loaded bortezomib induced significantly more apoptosis than did 1 nM of free bortezomib (P less than .01), and 10 nM of ceramide-loaded bortezomib brought about more cell death and apoptosis than did 10 nM of free bortezomib (P less than .05). These effects were likely the result of increased expression of proteins involved in apoptosis.
Liposomes might be able to boost the efficacy of bortezomib, according to the researchers, who are now studying the localization of these liposomes with confocal microscopes to better understand the mechanism of action.
“Such improvements,” they wrote, “offer the potential to reduce side effects known to occur with this chemotherapy, such as peripheral neuropathy, as well as to target Bort-resistant cancers.”