Ginsenoside compound K-bearing glycol chitosan conjugates: Synthesis, physicochemical characterization, and in vitro biological studies

•Compound K (CK) was conjugated to glycol chitosan through an acid-labile linkage.•The conjugates formed self-assembled nanoparticles in aqueous solutions.•It was stable for 8 days in pH 7.4, whereas they were degraded under acidic conditions.•The conjugates could release the CK rapidly under the acidic condition.•The conjugates exhibited higher cytotoxicity to HT29, HepG2, and HT22 cancer cells. Ginsenosides are triterpenoids found in Panax ginseng and have a numerous structural, functional, and pharmacological properties. The purpose of this study was to develop hydrophilic polymer functionalized ginsenoside conjugates to enhance water solubility and targeted delivery. To this end, hydrophobic ginsenoside compound K (CK) was covalently conjugated to the backbone of hydrophilic glycol chitosan (GC) through an acid-labile linkage. The resulting GC–CK conjugates formed self-assembled spherical nanoparticles in an aqueous solution, and their particles sizes were (296nm and 255nm) dependent on the degree of CK substitution. The nanoparticles were stable in the physiological buffer (pH 7.4) over a period of 8 days, whereas they were readily degraded under acidic conditions (pH 5.0) mimicking the intracellular pH-conditions. From in vitro release experiment, it was found that CK released slowly from the self-assembled nanoparticles in the physiological buffer (pH 7.4). On the other hand, the release rate of CK was rapidly increased under the acidic condition (pH 5.0). In vitro cytotoxicity assays revealed that GC–CK conjugates exhibited higher cytotoxicity than CK in HT29, and similar cytotoxicity in HepG2, and HT22 cell lines. Moreover, RAW264.7 cells treated with GC–CK maintained good cell viability and exhibited decreased lipopolysaccharide-induced NO production. Taken together, these results suggest that the GC–CK conjugate may be potentially useful as a tumor-specific delivery vehicle.