COS-Acyl) CGKRG Case Study

Part 5: Synthesis, characterization and evaluation of COS-SMCC-(fatty acyl) CGKRK as in vitro gene delivery system to MDA-231 The delivery of siRNA is a great challenge due to its susceptibility to serum nuclease digestion, quick renal clearance. In addition to its anionic charge which hampers its cellular uptake. Therefore, the success of the gene carrier system relays on, the design of a delivery system that can protect siRNA molecules from enzymatic degradation, the ability to translocate the gene into the cell releasing its payload, and effectively mediate the gene silencing pathway158. The cationic nature of chitosan and its derivatives has inspired the investigators to use them as promising non-viral gene vectors because of their less cytotoxicity, and immunogenicity, non-mutagenesis response in comparison with the viral vectors, polyarginine and polyethylene imine (PEI). As well as, their ability in the formation of stable
As we can see the particles size was varied by varying the polymer ratio, and the hydrophobic moiety immobilized on the COS chain. For the COS, and its oleoyl-CGKRK derivatives, the complexes showed increase in the size by increasing the polymer ratio from 1 to 5 folds. Increasing the polymer ratio to 10 folds resulted in a decrease in the size. Meanwhile, in the case of saturated fatty acids including the palmitoyl-CGKRK, and stearoyl-CGKRK derivatives of chitosan, they exhibited different pattern as the polymer: siRNA weight ratio increases from 1 to 5 the particle size decrease, then it increased when the weight ratio of polymer: siRNA reached 10. Additionaly, we noticed that among the chitosan derivatives oleiyl derivative had the smallest particle size at all polymer ratios. It is clear that, the fatty acid chain and its degree of hydrophilicity had a strong impact on the polymer/siRNA complexes size, figure