title: Amino acid-substituted gemini surfactant-based nanoparticles as safe and versatile gene delivery agents.
abstract: Gene based therapy represents an important advance in the treatment of diseases that heretofore have had either no treatment or cure. To capitalize on the true potential of gene therapy, there is a need to develop better delivery systems that can protect these therapeutic biomolecules and deliver them safely to the target sites. Recently, we have designed and developed a series of novel amino acid-substituted gemini surfactants with the general chemical formula C(12)H(25) (CH(3))(2)N(+)-(CH(2))(3)-N(AA)-(CH(2))(3)-N(+) (CH(3))(2)-C(12)H(25) (AA= glycine, lysine, glycyl-lysine and, lysyl-lysine). These compounds were synthesized and tested in rabbit epithelial cells using a model plasmid and a helper lipid. Plasmid/gemini/lipid (P/G/L) nanoparticles formulated using these novel compounds achieved higher gene expression than the nanoparticles containing the parent unsubstituted compound. In this study, we evaluated the cytotoxicity of P/G/L nanoparticles and explored the relationship between transfection efficiency/toxicity and their physicochemical characteristics (such as size, binding properties, etc.). An overall low toxicity is observed for all complexes with no significant difference among substituted and unsubstituted compounds. An interesting result revealed by the dye exclusion assay suggests a more balanced protection of the DNA by the glycine and glycyl-lysine substituted compounds. Thus, the higher transfection efficiency is attributed to the greater biocompatibility and flexibility of the amino acid/peptide-substituted gemini surfactants and demonstrates the feasibility of using amino acid-substituted gemini surfactants as gene carriers for the treatment of diseases affecting epithelial tissue.
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Canada.
authors.forename: Jagbir
authors.initials: J
authors.lastname: Singh
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Deborah
authors.initials: D
authors.lastname: Michel
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Verrall
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
authors.forename: Ildiko
authors.initials: I
authors.lastname: Badea
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D018929:Cell Culture Techniques; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D004847:Epithelial Cells; D015316:Genetic Therapy / Q000379:methods; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D011817:Rabbits; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D014162:Transfection / Q000379:methods*
chemical_list: D000596:Amino Acids; D008055:Lipids; D013501:Surface-Active Agents; D004247:DNA