Preparation of folate and carboxymethyl-β-cyclodextrin grafted trimethyl chitosan nanoparticles as co-carrier of doxorubicin and siRNA

Abstract In this paper, a novel grafted polymer (folate and carboxymethyl-β-cyclodextrin grafted trimethyl chitosan, FCT) was synthesized. Then the FCT nanoparticles (FCT NPs) were fabricated by ionic gelation and the potential of NPs as co-carrier of doxorubicin and siRNA was evaluated. The physicochemical properties of grafted polymer and NPs were characterized and analyzed by fourier transforms infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential and polydispersity index (PDI). The results showed the diameter of NPs ranged from 190 to 240 nm with polydispersity index of 0.192 and zeta potential of +21mv. The prepared NPs exhibited satisfactory drug loading capacity and encapsulation efficiency to doxorubicin and siRNA-survivin. Meanwhile, the prepared NPs could effectively protect siRNA-survivin from degradation of serum RNAase for a long time. Both drugs encapsulated in NPs all exhibited pH-dependent controlled sustained release characteristics and the cytotoxicity study testified that drug drug-loaded FCT NPs significantly improved the efficacy of antitumor drugs. The novel graft polymer was expected to become the co-carrier of anticancer and gene drugs in future with broad application prospects.