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

Yuan BO, Zhao Y, Dong S, Sun Y, Hao F, Xie J, Teng L, Lee RJ, Fu Y, Bi YE
Anticancer Res 39 237-243 01/01/2019


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 (AUC

CONCLUSION: These results suggest that R8-conjugated oleic acid-modified liposomes are effective delivery vehicles for glioma.

Full Text