Optimization Of Preparation Of Amphiphilic Block Copolymer Micelles By Supercritical Fluid Technology

Paclitaxel(PTX)is widely recognized as an efficient anticancer drug demonstrated to have the inhibition of tumors.Meanwhile,the biological application of PTX is limited by its poor solubility.In order to enhance the solubility and decrease adverse effects of paclitaxel,the drug delivery system based on nanoparticles and polymer have been developed.The traditional approaches of producing micelles mainly include emulsion solvent evaporation.There might be a little organic solvent residue in obtained micelles.Meanwhile,the evaporation of the organic solvent tends to bring serious pollution.In our experiment,we prepared polymer micelles loading PTX through solvent evaporation using supercritical carbon dioxide instead of traditional organic solvents.In order to determine the optimized process conditions,the effects of five parameters including:pressure,temperature,pressure release rate,volume ratio of water and SCCO2 and proportion of hydrophobic and hydrophilic blocks on the value of EE and LC were discussed in this study.The results showed that the temperature and the proportion of hydrophilic supercritical carbon dioxide segment and hydrophilic one have little effect on drug loading and entrapment efficiency.With the enhanced pressure and volume fraction of water and supercritical carbon dioxide,the drug loading and entrapment efficiency increased at relative low condition and then decreased.With the increasing release rate,the entrapment efficiency decreased continuously while the particle size became smaller.In this study,response surface analysis was used to optimize the three main factors including pressure,pressure release rate and volume ratio of water to SCCO2.By optimizing the analysis,we gained the fitting equation and the 3D graph that the three factors on drug loading and encapsulation efficiency.The experiment chose BBD as the surface methodology design and 17 experiments were carried out.Based on the fitting equation,the optimization process conditions pressure was 12.27MPa,pressure release rate was lOL/min,volume ratio of water to SCCO2 was 3.67:1,respectively.The LC was 71.0%under the optimization conditions.The verification experiment under the conditions was carried out and the LC of the obtained micelles was 70.7%which was consistent with the fitting result.According to the TEM image of the micelles prepared under the optimization process conditions,the micelle size was between 200 and 400 nm and the shape was a regular round.The prepared micelles were used for in vitro release experiments.The drug release was fast in the beginning and then tended to be smooth.The total values drug release amount was about 80%in 120 hours when the temperature was 37? and the values of pH was 7.4.