RVG29-modified docetaxel-loaded nanoparticles for brain-targeted glioma therapy.

Abstract

Gliomas are the most common malignant brain tumor, but treatment is limited by the blood-brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-(d,l-lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method. The NPs were approximately 110 nm and had smooth surfaces. Enzyme-linked immunoassay results showed that the amount of receptor on the surface of glioma cells was 2.04-fold higher than that of nonmalignant cells, which may promote accumulation of RVG29-modified NPs at the targeting site. NPs showed targeting properties for glioma cells compared with the non-targeting NPs in an in vitro cellular uptake test. Targeted NPs also showed better BBB penetration in an in vitro model. In vivo tests indicated that RVG29-PEG-PLGA-NPs could selectively accumulate in intracranial glioma tissue. In conclusion, these results indicated that the RVG29-modified NPs have potential efficacy for glioma therapy.

• Authors: Hongchen Hua, Xuemei Zhang, Hongjie Mu, Qingqing Meng, Ying Jiang, Yiyun Wang, Xiaoyan Lu, Aiping Wang, Sha Liu, Yaping Zhang, Zhihui Wan, Kaoxiang Sun
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 543 Issue 1-2 Pg. 179-189 (May 30 2018) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 29555442 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Glycoproteins
• Peptide Fragments
• Taxoids
• Viral Proteins
• rabies virus glycoprotein peptide
• Docetaxel

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Brain (metabolism)
• Brain Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Docetaxel
• Drug Delivery Systems
• Glioma (drug therapy, metabolism)
• Glycoproteins (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Male
• Mice
• Nanoparticles (administration & dosage, chemistry, therapeutic use)
• Peptide Fragments (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Rats, Sprague-Dawley
• Taxoids (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Tissue Distribution
• Viral Proteins (administration & dosage, chemistry, pharmacokinetics, therapeutic use)