Synthesis, Preparation and Evaluation of Doxorubicin-Loaded Chitosan Oligosaccharide/Indomethacin Nanoparticles.

Doxorubicin(DOX)-loaded chitosan oligosaccharide(CSO)/indomethacin(Indo) nanoparticles(NPs) was developed as a uniform particle size, high drug loaded capacity, good biostability and biocompatibility drug delivery system. According to the principle of “Like dissolves like”, Indo was grafted to the bones of CSO under mild condition. The CSO/Indo NPs were formed by ultrasonic dispersion method in the aqueous medium. The critical aggregation concentrations of the CSO/Indo NPs were from 33.89 µg/ml to 287.92 µg/ml. The IC50 of blank CSO/Indo NPs (311.06 µg/ml–1365.3 µg/ml) on HepG2 cell lines indicated that they could be used as safe carriers except CSO18000/Indo100%. DOX–loaded NPs were prepared by a dialysis method. The sizes of drug-loaded NPs were significantly smaller than those of the corresponding blank nanoparticles while all the zeta potentials of drug-loaded nanoparticles were lower than those blank nanoparticles. These data supported our original scientific hypothesis that the π bonds in the structure of CSO/Indo might generate the physical interaction with the π bonds of DOX. Compared with the IC50 of free DOX·HCl solution (8.576 µg/ml), the IC50 of the drug-loaded NPs (3.125 µg/ml—4.524 µg/ml) showed that they had obvious enhanced anti-tumour effect. Therefore, CSO/Indo NPs provided a new choice for insoluble anticancer drugs.Graphic Abstract: Doxorubicin(DOX)-loaded chitosan oligosaccharide(CSO)/indomethacin(Indo) nanoparticles(NPs) was developed as a uniform particle size, high drug loaded capacity, good biostability and biocompatibility drug delivery system. According to the principle of “Like dissolves like”, Indo was grafted to the bones of CSO under mild condition. The CSO/Indo NPs were formed by ultrasonic dispersion method in the aqueous medium. The critical aggregation concentrations of the CSO/Indo NPs were from 33.89 µg/ml to 287.92 µg/ml. The IC50 of blank CSO/Indo NPs (311.06 µg/ml–1365.3 µg/ml) on HepG2 cell lines indicated that they could be used as safe carriers except CSO18000/Indo100%. DOX–loaded NPs were prepared by a dialysis method. The sizes of drug-loaded NPs were significantly smaller than those of the corresponding blank nanoparticles while all the zeta potentials of drug-loaded nanoparticles were lower than those blank nanoparticles. These data supported our original scientific hypothesis that the π bonds in the structure of CSO/Indo might generate the physical interaction with the π bonds of DOX. Compared with the IC50 of free DOX·HCl solution (8.576 µg/ml), the IC50 of the drug-loaded NPs (3.125 µg/ml—4.524 µg/ml) showed that they had obvious enhanced anti-tumour effect. Therefore, CSO/Indo NPs provided a new choice for insoluble anticancer drugs. [ABSTRACT FROM AUTHOR]