A novel PEGylation of chitosan nanoparticles for gene delivery

Abstract

CS (chitosan) has emerged as a promising non-viral vector for gene delivery because of its ability to form complexes with pDNA (plasmid DNA) and enhance its transport across cellular membranes through endocytosis. Complexes of CS and pDNA may improve transfection efficiency; however, they are not capable of sustained DNA release and prolonging gene transfer. In order to achieve prolonged delivery of CS-DNA complexes, we prepared CS NP (nanoparticle) and CS-DNA complexes. alpha-Methoxy-omega-succinimidylpoly(ethylene glycol) was then conjugated to the surface of CS-DNA complexes using an active ester scheme; finally, the potential of PEGylation [poly(ethylene glycol)ylation] of CS NP as a non-viral gene-delivery vector to transfer exogenous genes in vitro and in vivo were examined. Electrophoretic analysis suggested that CS NPs could protect the DNA from nuclease degradation. The pDNA carried by CS NPs could enter and be expressed in HepG2 cells. However, the transfection efficiency was very low and the highest dose of DNA transferred was 1.6 microg. The transfection activities of CS-DNA-PEG were preserved and a higher dose (2.4 microg) of pDNA was transferred. This indicated that the transfection efficiency of the PEGylated complexes had been improved. In vivo experiments also showed that CS-DNA-PEG complexes mediated higher gene expression in tissues than did CS-DNA complexes, and that gene expression in tumours induced by CS-DNA-PEG complexes was the highest of all. These results suggested that PEGylation of CS-DNA complexes improves non-viral gene delivery in vitro or in vivo and has the potential to deliver therapeutic genes directly into hepatoma tissues.

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

“…To make chitosan more water soluble and enhance its blood-circulation time, conjugation of poly-ethylene glycol (PEG) polymer with chitosan is a common approach [50]. The PEGylated nanoparticle is generally known as “stealth” nanoparticle.…”

Nanoparticles for drug delivery to the anterior segment of the eye

“…The penetration mechanisms for nanoparticles into the interior segment of the eye have not been deeply studied; however, the commonly accepted endocytosis mechanism in explaining nanoparticles’ tissue penetration was also observed by Robinson and his colleagues when they used fluorescence microscopy to study the penetration of poly(butyl cyanoacrylate) nanoparticles across the ex vivo rabbit cornea and conjunctiva [46, 49–54]. The most commonly used in vitro and ex vivo models for evaluating the corneal penetration have been summarized by Agarwal et al [55].…”

Discovery of Cationic Polymers for Non-Viral Gene Delivery Using Combinatorial Approaches

“…Although chitosan possesses several inherent advantages including biocompatibility, biodegradability and low toxicity, properties like poor solubility, low transfection efficiencies, and low cell specificities limit their potential as gene delivery carriers. To improve the solubility and transfection efficiency of chitosan, Zhang et al[70] developed PEGylated chitosan that exhibited higher transfection efficiency than the CS-DNA complexes in HepG2 (hepatocellular carcinoma) cells both in vitro and in vivo .…”