✦ LIBER ✦

Hydrophobically modified low molecular weight chitosans as efficient and nontoxic gene delivery vectors

✍ Scribed by Xin Zhang; Sebnem Ercelen; Guy Duportail; Emmanuel Schaub; Vladimir Tikhonov; Alexander Slita; Vladimir Zarubaev; Valery Babak; Yves Mély

Publisher: John Wiley and Sons
Year: 2008
Tongue: English
Weight: 927 KB
Volume: 10
Category: Article
ISSN: 1099-498X
DOI: 10.1002/jgm.1167

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Background

Chitosan derivatives are potential candidates for gene delivery because they are biocompatible and low toxic. However, their use has been limited by their moderate transfection efficiency and the rather large sizes of DNA complexes with high molecular weight chitosans. To circumvent these limitations, we used low molecular weight (approximately 5 kDa) chitosans grafted at 3 and 18 mol% with N‐/2(3)‐(dodec‐2‐enyl)succinoyl groups (HM‐LMW‐ch) that exhibit surfactant‐like properties.

Methods

The physico‐chemical properties of complexes of DNA with the two HM‐LMW‐ch derivatives and the nonmodified LMW‐ch were compared by electrophoresis, dynamic light scattering, fluorescence spectroscopy and fluorescence correlation spectroscopy. Moreover, their transfection efficiencies and cytotoxicity were evaluated and their intracellular trafficking was monitored by confocal microscopy. Finally, their ability to deliver genes in mice kidneys after systemic administration was investigated.

Results

Complexes with HM(3%)‐LMW‐ch, but not with HM(18%)‐LMW‐ch and LMW‐ch, efficiently delivered genes in mice kidneys. HM(3%)‐LMW‐ch formed small positively charged particles that were resistant to DNases and nucleases and marginally interact with serum components. Moreover, these particles were efficiently internalized in cells and low toxic. By contrast, HM(18%)‐LMW‐ch formed large and weakly charged aggregates with DNA that were highly susceptible to DNases and nucleases.

Conclusions

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