Cell-penetrating Peptide-coated Liposomes for Drug Delivery Across the Blood-Brain Barrier

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 mu M after 24 h treatment. The biodistribution of doxorubicin in the brain was significantly improved by R8PLP. The area under the concentration-time curve (AUC(0.5-12 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.