Cationic/Anionic Polyelectrolyte (PLL/PGA) Coated Vesicular Phospholipid Gels (VPGs) Loaded with Cytarabine for Sustained Release and Anti-glioma Effects

Abstract

Background

Cationic and anionic polymer-modified nanoparticles offer promising properties for the drug and gene delivery. Our study uses cationic/anionic polyelectrolyte coated vesicular phospholipid gels (VPGs) loaded with cytarabine (Ara-C) that enhance in vitro and in vivo anti-glioma effects.

Methods

Sodium cholesteryl sulfate (SCS) or octadecylamine (ODA) incorporated in a phospholipids phase were used to prepare charged VPGs, and cationic ε-polylysine (PLL) coated VPGs (PLL-SCS VPGs) and anionic γ-polyglutamic acid (PGA) coated VPGs (PGA-ODA VPGs) were prepared via electrostatic interactions, respectively. The morphology, particle size, zeta potential, rheology properties, and in vitro release were then characterized. The in vitro cytotoxicity and cellular uptake were evaluated on U87-MG glioma cells. The in vivo antitumor effects were studied on BALB/c nude mice bearing a right flank U87-MG glioma model.

Results

The TEM images and physicochemical properties of cationic/anionic polyelectrolyte coated VPGs exhibited that polymers covered on the vesicular surface. The results of rheologic property analysis showed that cationic/anionic polyelectrolyte coated VPGs enhanced the viscosity of uncoated VPGs. The in vitro release experiments revealed that cationic/anionic polyelectrolyte coated VPGs kept Ara-C sustained release up to 18 days. Specially, compared with PLL-SCS VPGs, PGA-ODA VPGs demonstrated higher in vitro cytotoxicity and cellular uptake efficiency in U87-MG glioma cells, and enhanced in vivo antitumor effects when subcutaneously injected around the tumor. No severe toxicity appeared in the right flank U87-MG glioma model of BALB/c nude mice.

Conclusion

Anionic γ-PGA coated VPGs were superior to cationic PLL coated VPGs in terms of improving the anti-glioma effect for local delivery.

Keywords:

• biodegradable depots
• polyelectrolyte coating
• sustained release
• glioma
• local therapy

Acknowledgments

This project is financially supported by the National Natural Science Foundation of China (NO. 81560655, NO. 81860707, NO. 81572797), the Natural Science Foundation of Guangdong Province (NO. 2016A030311015), the Natural Science Foundation of Guangxi Province (NO. 2017GXNSFAA198061) and the Cultivation Plan of One Thousand Young and Middle-aged Key Teachers in Colleges and Universities of Guangxi. We are grateful to Danielle for English editing.

Disclosure

The authors report no conflicts of interest in this work.