title: Interfacial engineering of pyridinium gemini surfactants for the generation of synthetic transfection systems.
abstract: Pyridinium gemini surfactants possess a soft charge, a high charge/mass ratio and a high molecular flexibility - all key parameters that recommend their use in synthetic gene delivery systems with in vitro and in vivo efficiency. In present study we generated a DNA delivery system through interfacial engineering of pyridinium gemini surfactants at the level of linker, hydrophobic chains and counterions. The self-assembling of the pyridinium amphiphiles and the physicochemical properties of the resultant supra-molecular assemblies were studied in bulk and in solution through a combination of techniques that included DSC, X-ray diffraction, polarized microscopy, CMC, dynamic light scattering and zeta potential measurements. We assessed the impact of different structural elements and formulation parameters of these pyridinium amphiphiles on their DNA compaction properties, transfection efficiency, cytotoxicity, in a complete structure-activity relationship study. This interfacial engineering process generated transfection systems with reduced cytotoxicity and high transfection efficiency in media containing elevated levels of serum that mimic the in vivo conditions.
authors.affiliation: Department of Pharmaceutical Sciences and Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, 3307 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Vishnu D
authors.initials: VD
authors.lastname: Sharma
authors.forename: Eronmwon O
authors.initials: EO
authors.lastname: Aifuwa
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heiney
authors.forename: Marc A
authors.initials: MA
authors.lastname: Ilies
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018014:Gene Transfer Techniques / Q000009:adverse effects; D006801:Humans; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000009:adverse effects / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000009:adverse effects / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D011726:Pyridinium Compounds; D013501:Surface-Active Agents