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Di-Peptide-Modified Gemini Surfactants as Gene Delivery Vectors: Exploring the Role of the Alkyl Tail in Their Physicochemical Behavior and Biological Activity
- Source :
- The AAPS journal. 18(5)
- Publication Year :
- 2016
-
Abstract
- The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out. Characterization of the nano-assemblies was accomplished by measuring the particle size and surface charge. Morphological characteristics and lipid organization were studied by small angle X-ray scattering technique. Lipid monolayers were studied using a Langmuir-Blodgett trough. The highest activity of glycyl-lysine modified gemini surfactants was observed with the 16-carbon tail compound at 2.5 N/P ratio, showing a 5- to 10-fold increase in the level of reporter protein compared to the 12 and 18:1 carbon tail compounds. This ratio is significantly lower compared to the previously studied gemini surfactants with alkyl or amino- spacers. In addition, the 16-carbon tail compound exhibited the highest cell viability (85%). This high efficiency is attributed to the lowest critical micelle concentration of the 16-tail gemini surfactant and a balanced packing of the nanoparticles by mixing a saturated and unsaturated lipid together. At the optimal N/P ratio, all nanoparticles exhibited an inverted hexagonal lipid assembly. The results show that the length and nature of the tail of the gemini surfactants play an important role in determining the transgene efficiency of the delivery system. We demonstrated here that the interplay between the headgroup and the nature of tail is specific to each series, thus in the process of rational design, the contribution of the latter should be assessed in the appropriate context.
- Subjects :
- Chemical Phenomena
Cell Survival
Genetic Vectors
Pharmaceutical Science
Context (language use)
02 engineering and technology
010402 general chemistry
01 natural sciences
Structure-Activity Relationship
Surface-Active Agents
Pulmonary surfactant
Monolayer
Chlorocebus aethiops
Organic chemistry
Animals
Surface charge
Alkyl
chemistry.chemical_classification
Degree of unsaturation
Small-angle X-ray scattering
Chemistry
Gene Transfer Techniques
Dipeptides
021001 nanoscience & nanotechnology
0104 chemical sciences
Critical micelle concentration
COS Cells
Biophysics
0210 nano-technology
Subjects
Details
- ISSN :
- 15507416
- Volume :
- 18
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The AAPS journal
- Accession number :
- edsair.doi.dedup.....ae0dfe589c224e5d34eca8c041ac352a