Application of a simple desolvation method to increase the formation yield, physical stability and hydrophobic drug encapsulation capacity of chitosan-based nanoparticles

Abstract

As one of the classical nano drug carriers, chitosan-based nanoparticles (CsNps) are getting increasing attentions for their non-toxicity, biocompatibility and biodegradability. The ionotropic gelation is the most favorable method for CsNps preparation, while it’s beset by some issues, i.e. low particle formation yield, poor physical stability and low hydrophobic drug loading capacity. To solve these problems, a simple desolvation method was attempted in this study for CsNps preparation. Using this method, an increased formation yield of CsNps (about 100%) could be obtained, and after diluting the particles by various buffers (PBS 7.0, 7.4 and 8.0, DMEM medium and 1640 medium), an improved stability in diameter could be observed. The drug loading results showed paclitaxel loading efficiency of 9.8% could be obtained when the ratio of paclitaxel to Cs was set at 0.2, higher than the ionotropic gelation method (0.43%). The particles formation mechanisms were studied by the molecular dynamics simulation, and the results showed the Lennard-Jones interaction of Cs-Cs, which could be adjusted by the pH value of system, played a great role in formation of particles with the desolvation method. This study provided an alternative preparation technology for CsNps with high process yield, physical stability and hydrophobic drug encapsulation capacity.