Comparison of three water-soluble polyphosphate tripolyphosphate, phytic acid, and sodium hexametaphosphate as crosslinking agents in chitosan nanoparticle formulation

Chitosan nanoparticles (CS-NPs) prepared by ionic gelation with tripolyphosphate (TPP) are a promising drug carrier for mucosal administration due to their remarkable mucoadhesivity and biocompatibility. In this work, CS-NPs were obtained by an ionotropic gelation method with polyphosphate crosslinking agents of tripolyphosphate (TPP), phytic acid (PA), and sodium hexametaphosphate (SHMP). The drug encapsulation efficiency, in vitro drug release behavior, mucoadhesivity, and cytotoxicity of the CS-NPs were evaluated. The results demonstrated that the high concentration of H+ ion would impede the formation of CS-TPP-NPs but promote the formation of CS-PA-NPs and CS-SHMP-NPs. The obtained CS-NPs were approximately spherical in shape, biocompatible confirmed by the cytotoxicity test, and bioadhesive particles with a narrow diameter distribution (0.20 +/- 0.02 of polydispersity index) less than 200 nm. The encapsulation efficiency of myricetin (MYR) in CS-NPs crosslinked by PA and SHMP (67.3 +/- 0.4 % and 62.2 +/- 0.2 %) was significantly higher than that in CS-NPs crosslinked by TPP (47.7 +/- 0.1 %) (p < 0.05); their drug release rate (43.7 +/- 5.1 % and 44.0 +/- 3.7 %) was also significantly slower than that of MYR-CS-NPs crosslinked by TPP (103.4 +/- 4.0 %) (p < 0.05). Furthermore, a strong mucoadhesiveness of the CS-NPs crosslinked by PA was shown by a fast increase of the turbidity value and a sharp decrease of the zeta potential in the mucin solution test.