Effect of different mass ratio of PLA: PEG segments in PLA-PEG-PLA copolymers on the physicochemical characterization and DNA release profile

Adapting controlled release technologies to the delivery of DNA has the great potential to overcome extracellular barriers that limit gene delivery. This study aims at investigating the effect of different mass ratio of PLA: PEG in the various tri block poly (lactic acid)-poly (ethylene glycol) - Poly (lactic acid) copolymer (PLA-PEG-PLA) on the properties of the resulting nanoparticles. The various tri block PLA-PEG-PLA copolymers were prepared via ring-opening polymerization by poly (ethylene glycol) (PEG), lactic acid and stannous octoate as raw material and catalyst, respectively. DNA or siRNA-FAM was incorporated into the tree block PLA-PEG-PLA copolymer using double emulsion solvent evaporation technique. Properties of these nanoparticles, such as morphology and particles size of nanoparticles, DNA release kinetics, in vitro cytotoxicity and siRNA-FAM transfer efficiency were evaluated.  Scanning electron microscope (SEM) showed that PLA-PEG-PLA/DNA nanoparticles have spherical morphology with smooth surface. Dynamic light scattering results showed the particle size of PLA–PEG-PLA copolymers increased with an increase in the mass ratio of PLA in PLA-PEG-PLA copolymers. The release profile of the PLA-PEG-PLA/DNA nanoparticles measured using nanodrop and the results showed that, decrease in mass ratio of PLA, increased the release profile of DNA from PLA-PEG-PLA/DNA nanoparticles. Moreover the percentage of siRNA-FAM transfer to MCF-7 cells by various PLA-PEG-PLA copolymers, measuring using flow cytometry and fluorescence microscopy. These results showed that there is same relation between the mass ratio of PLA and percentage of siRNA-FAM delivery into the MCF-7 cells.