Gelucire-stabilized nanoparticles as a potential DNA delivery system.
Clinical viability of gene delivery systems has been greatly impacted by potential toxicity of the delivery systems. Recently, we reported the nanoparticle (NP) preparation process that employs biocompatible materials such as Gelucire® 44/14 and cetyl alcohol as matrix materials. In the current study, the NP preparation was modified for pDNA loading through: (i) inclusion of cationic lipids (DOTAP or DDAB) with NP matrix materials; or (ii) application of cationic surfactants (CTAB) to generate NPs with desired surface charges for pDNA complexation. Colloidal stability and efficiency of loading pGL3-DR4X2-luciferase plasmid DNA in NPs were verified by gel permeation chromatography. Compared to pDNA alone, all the NPs were effective in preserving pDNA from digestion by DNase. While pDNA loading using CTAB-NPs involved fewer steps compared to DOTAP-NPs and DDAB-NPs, CTAB-NPs were greatly impacted by elevated cytotoxicity level which could be ascribed to the concentrations of CTAB in NP formulations. In vitro transfection studies (in HepG2 cells) based on luciferase expression showed the ranking of cell transfection efficiency as DOTAP-NPs > DDAB-NPs > CTAB-NPs. The overall work provided an initial assessment of gelucire-stabilized NPs as a potential platform for gene delivery.
a Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , OH , USA.
Moses O
MO
Oyewumi
a Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , OH , USA.
Daniel
D
Wehrung
a Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , OH , USA.
Prabodh
P
Sadana
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry
C104509:gelucire 44-14; D011092:Polyethylene Glycols; D004247:DNA
Cationic lipids; gene therapy; macrophage activation; nanoparticles; transfection