Title:Self-Assembled Nanoparticle-Forming Derivatives of Dextrin-Conjugated Polyethylenimine Containing Urethane Bonds for Enhanced Delivery of Interleukin-12 Plasmid
Volume: 21
Issue: 1
Author(s): Valiollah Keshavarz, Maryam Kazemi, Bahman Khalvati, Ali Dehshahri*Hossein Sadeghpour*
Affiliation:
- Department of Pharmaceutical Biotechnology,
School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords:
Gene delivery, polyethylenimine (PEI), nanoparticle, transfection, dextrin, urethane.
Abstract:
Background and Objective: In the present investigation, low molecular weight polyethylenimine
(LMW PEI, 1.8 kDa PEI) was conjugated to dextrin via urethane units and tested
to transfer plasmid encoding interleukin-12 (IL-12) plasmid. Although high molecular weight
PEI (HMW PEI, 25 kDa PEI) has shown substantial transfection efficiency, its wide application
has been hampered due to considerable cytotoxicity. Therefore, LMW PEI with low toxic effects
was used as the core of our gene transfer construct.
Methods: LMW PEI was conjugated to dextrin via urethane units to improve its biophysical
characteristics as well as cytotoxic effects. The conjugates were characterized in terms of buffering
capacity, plasmid DNA condensation ability, particle size, and zeta potential as well as protection
against enzymatic degradation. In Vitro experiments were carried out to evaluate the
ability of these LMW PEI conjugates to transfer plasmid encoding human interleukin-12 (hIL-
12) to the cells. The MTT assay was performed to measure the cell-induced toxicity of the conjugates.
Results: The results of our study demonstrated that the PEI derivatives with higher amounts of
amine content (i.e. higher conjugation degrees) have considerable buffering capacity and plasmid
condensation ability. These conjugates could condense plasmid DNA at Carrier to Plasmid
ratios (C/P) ≥2 and form polyplexes at the size range of 120-165 nm while their zeta potential
was around 5.5-8.5 mV. The results of transfection efficiency demonstrated that the level of IL-
12 production increased by 2-3 folds compared with unmodified LMW PEI while the level of
cytotoxicity was not higher than 20%.
Conclusion: The strategy used in this study shows a promising way to prepare gene carriers
with high transfection efficiency and low toxicity.
