title: Ginsenoside compound K-bearing glycol chitosan conjugates: synthesis, physicochemical characterization, and in vitro biological studies.
abstract: 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 (296 nm and 255 nm) 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.
authors.affiliation: Graduate School of Biotechnology and Ginseng Bank, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea. Electronic address: ramyabinfo@gmail.com.
authors.forename: Ramya
authors.initials: R
authors.lastname: Mathiyalagan
authors.affiliation: Graduate School of Biotechnology and Ginseng Bank, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea; Insilicogen Inc., #909, Venture Valley, 958, Gosaek-dong, Gwonseon-gu, Suwon, Gyeonggi-do 441-813, South Korea. Electronic address: s.sathiyamurthi@gmail.com.
authors.forename: Sathiyamoorthy
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: Graduate School of Biotechnology and Ginseng Bank, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea. Electronic address: yeonjukim@khu.ac.kr.
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea. Electronic address: yckim@wonkwang.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology and Ginseng Bank, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea. Electronic address: dcyang@khu.ac.kr.
authors.forename: Deok Chun
authors.initials: DC
authors.lastname: Yang
mesh_terms: D002021:Buffers; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D036145:Ginsenosides / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size
chemical_list: D002021:Buffers; D048271:Chitosan; D036145:Ginsenosides; C118638:glycol-chitosan; C112772:ginsenoside compound K
keywords: Anti-cancer efficacy; Compound K; Ginsenosides; Glycol chitosan; Self-assembled nanoparticles; Tumor