ABSTRACT
BACKGROUND/AIM: Glioma is a deadly form of brain cancer. Doxorubicin is cytotoxic against glioma cells. However, the blood-brain barrier (BBB) limits its ability to be delivered to the brain. MATERIALS AND METHODS: Liposomes (R8PLP) formed from, 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (PEG-DSPE), cholesterol and egg phosphatidylcholine (ePC) were modified by cell-penetrating peptide R8 conjugated with oleic acid as a novel method for delivering doxorubicin. The antitumor effect of R8PLP was evaluated by uptake, cytotoxicity and brain accumulation. RESULTS: The size of R8PLP was 95 nm. Doxorubicin was loaded into R8PLP by active loading with more than 95% encapsulation efficiency. Cellular uptake of R8PLP by U87-MG cells was 8.6-fold higher than that of unmodified liposomes. R8PLP reduced cell viability by 16.18% and 18.11% compared to cholesterol-ePC-liposomes and free doxorubicin, respectively, at 3.6 µM after 24 h treatment. The biodistribution of doxorubicin in the brain was significantly improved by R8PLP. The area under the concentration-time curve (AUC0.5-12 h) of R8PLP was 2.4-times higher than that of cholesterol-ePC-PEG-DSPE-liposomes. CONCLUSION: These results suggest that R8-conjugated oleic acid-modified liposomes are effective delivery vehicles for glioma.
Subject(s)
Cell-Penetrating Peptides/administration & dosage , Drug Delivery Systems , Glioma/drug therapy , Nanoparticles/administration & dosage , Blood-Brain Barrier/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell-Penetrating Peptides/chemistry , Cholesterol/chemistry , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Fatty Acids, Monounsaturated/chemistry , Glioma/pathology , Humans , Liposomes/administration & dosage , Liposomes/chemistry , Nanoparticles/chemistry , Phosphatidylcholines/chemistry , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Quaternary Ammonium Compounds/chemistry , Tissue Distribution/drug effectsABSTRACT
BACKGROUND/AIM: Cordycepin is an endogenous nucleoside with significant anticancer biological activity. The objective of this study was to develop targeted liposomes to improve solubility and biological activity of cordycepin. MATERIALS AND METHODS: We established transferrin-conjugated liposomes to deliver cordycepin to liver cancer cells and evaluated the uptake and effect. RESULTS: The liposomes were loaded with cordycepin. Their average size was 125.3 nm, with drug encapsulation efficiency of 65.3%. The liposomes had good colloidal stability and released cordycepin slowly. Liposomal cordycepin was shown to increase reactive oxygen species production and cause depolarization of the mitochondrial transmembrane in liver cancer cells. Cellular uptake of liposomal cordycepin was enhanced by conjugation to transferrin, that facilitated receptor-mediated endocytosis. CONCLUSION: Transferrin-conjugated liposomes are effective as nanocarriers for cordycepin delivery to liver cancer cells.
