Modifying Cationic Liposomes with Cholesteryl-PEG Prevents Their Aggregation in Human Urine and Enhances Cellular Uptake by Bladder Cancer Cells.
Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs. When 2 mol% of PEG2k lipids were introduced, the lipid structures of 1,2-distearoly-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-distearoyl-sn-glycerol (DSG) greatly prevented aggregation compared with cholesterol. By contrast, when Cat-LPs, after incubation in urine, were exposed to bladder cancer cells, only introducing cholesteryl-PEG into the Cat-LPs showed a significant enhancement in cellular uptake. These results offer the potential for incorporating cholesteryl-PEG into Cat-LPs for achieving both stability in urine and effective cellular uptake.
Faculty of Pharmaceutical Sciences, Hokkaido University.
Takashi
T
Nakamura
Yosuke
Y
Noma
Yu
Y
Sakurai
Hideyoshi
H
Harashima
D000818:Animals; D002412:Cations; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D004355:Drug Stability; D006801:Humans; D008081:Liposomes; D051379:Mice; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; C118255:polyethylene glycol-cholesterol; D011092:Polyethylene Glycols; D002784:Cholesterol