Arginine-Glycine-Aspartic Acid-Modified Lipid-Polymer Hybrid Nanoparticles for Docetaxel Delivery in Glioblastoma Multiforme.

Abstract

Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of the anticancer drug, docetaxel. Transmission electron microscopic observations confirmed the presence of a lipid coating over the polymeric core. Using coumarin-6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA-nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6 cells overexpressing integrin α(v)β3. The anti-proliferative activity of docetaxel-loaded RGD-L-P against C6 cells was increased 2.69- and 4.13-fold compared with L-P and PLGA-P, respectively. Regarding biodistribution, the strongest brain-localized fluorescence signals were detected in glioblastoma multiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30-tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43, 1.78, 3.35, and 3.56 compared with animals given L-P (P < 0.05), PLGA-P (P < 0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively, these results support RGD-L-P as a promising drug delivery system for the specific targeting and the treatment of GBM.

• Authors: Kairong Shi, Jin Zhou, Qianyu Zhang, Huile Gao, Yayuan Liu, Taili Zong, Qin He
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 3 Pg. 382-91 (Mar 2015) ISSN: 1550-7033 [Print] United States
• PMID: 26307822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Nanocapsules
• Oligopeptides
• Polymers
• Taxoids
• Docetaxel
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Diffusion
• Docetaxel
• Glioblastoma (drug therapy, metabolism, pathology)
• Lipids (chemistry)
• Nanocapsules (chemistry, ultrastructure)
• Nanocomposites (chemistry, ultrastructure)
• Oligopeptides (chemistry, pharmacokinetics)
• Polymers (chemistry)
• Rats
• Rats, Sprague-Dawley
• Survival Rate
• Taxoids (administration & dosage, chemistry)
• Treatment Outcome