title: Enhanced transfection efficiency and reduced cytotoxicity of novel lipid-polymer hybrid nanoplexes.
abstract: The present study reports the development, characterization, and evaluation of novel polyelectrolytes stabilized lipoplexes as a nonviral vector for gene delivery. In order to achieve the advantage of both DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and PEI (high transfection efficiency) a system was hypothesized in which DOTAP/phosphatidyl choline (PC) lipoplexes were electrostatically coated with anionic poly(acrylic acid) (PAA) and cationic polyethylenimine (PEI) alternatively to finally shape a robust structure PEI-PAA-DOTAP/PC-lipoplexes (nanoplexes). The nanoplexes were found to have size of 242.6 ± 9.4 nm and zeta potential of +23.1 ± 1.5 mV. Following development nanoplexes were evaluated for cellular uptake, nuclear colocalization, transfection efficiency, and cellular toxicity in MCF-7, HeLa, and HEK-293 cell lines. In support of our hypothesis nanoplexes exhibited higher uptake and nuclear colocalization in comparison with DOTAP/PC, DOTAP/DOPE lipoplexes, and PEI polyplexes. Nanoplexes also exhibited 50-80, 11-12, 6-7, and 5-6 fold higher transfection efficiency in comparison with DOTAP/PC-lipoplexes, DOTAP/DOPE-lipoplexes, PEI-polyplexes, and lipofectamine, respectively, and significantly lower toxicity in comparison with DOTAP/PC, DOTAP/DOPE lipoplexes, PEI polyplexes, and commercial lipofectamine.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab-160062, India. sanyogjain@niper.ac.in
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Agrawal
authors.forename: Kaushik
authors.initials: K
authors.lastname: Thanki
authors.forename: Uttam Chand
authors.initials: UC
authors.lastname: Banerjee
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000180:Acrylic Resins; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; C086724:Lipofectamine; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C006903:carbopol 940; D011094:Polyethyleneimine; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane