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

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.

• Authors: B O Yuan, Yarong Zhao, Shiyan Dong, Yating Sun, Fei Hao, Jing Xie, Lesheng Teng, Robert J Lee, Yaowen Fu, Y E Bi
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 1 Pg. 237-243 (Jan 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 30591464 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Cell-Penetrating Peptides
• Fatty Acids, Monounsaturated
• Liposomes
• Phosphatidylcholines
• Phosphatidylethanolamines
• Quaternary Ammonium Compounds
• polyethylene glycol-distearoylphosphatidylethanolamine
• Polyethylene Glycols
• Doxorubicin
• Cholesterol
• 1,2-dioleoyloxy-3-(trimethylammonium)propane

Topics

• Blood-Brain Barrier (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cell-Penetrating Peptides (administration & dosage, chemistry)
• Cholesterol (chemistry)
• Doxorubicin (administration & dosage, chemistry)
• Drug Delivery Systems
• Fatty Acids, Monounsaturated (chemistry)
• Glioma (drug therapy, pathology)
• Humans
• Liposomes (administration & dosage, chemistry)
• Nanoparticles (administration & dosage, chemistry)
• Phosphatidylcholines (chemistry)
• Phosphatidylethanolamines (chemistry)
• Polyethylene Glycols (chemistry)
• Quaternary Ammonium Compounds (chemistry)
• Tissue Distribution (drug effects)