title: Protopanaxadiol aglycone ginsenoside-polyethylene glycol conjugates: synthesis, physicochemical characterizations, and in vitro studies.
abstract: Ginsenosides are triterpenoid saponins, which is an active compound responsible for most of the pharmacological effects of ginseng (Panax ginseng Meyer). It is known to have numerous structural and pharmacological properties. However, aqueous solubility and delivery of ginsenosides in targeted region by avoiding undesirable toxicity to normal cell is also of prime importance. The aim of this study was to obtain amphiphilic ginsenoside derivatives in which hydrophilic polymers were conjugated to ginsenosides to enhance the water solubility and targeted delivery. To this end, the hydrophobic protopanaxadiol ginsenoside aglycone (aPPD) was covalently conjugated to the backbone of hydrophilic polyethylene glycol (PEG) through a pH sensitive ester linkage, which was confirmed by1H NMR and FTIR. The resultant PPD is covalently conjugated to hydrophilic PEG through esterification (PEG-PPD) forming self-assembled spherical nanoparticles, whose average particle diameter was 189 nm as observed by FE-TEM and particle size analyzer respectively. In vitro release experiments revealed that the release rate of PPD was rapidly increased from the self-assembled nanoparticles under acidic conditions (pH 5.0) than in a physiological buffer (pH 7.4) condition. Furthermore, in vitro cytotoxicity assays revealed that PEG-PPD conjugates exhibited lower cytotoxicity in HT-29 cancer cells compared with PPD alone. Since the slow release of PPD from conjugates is triggered only by acidic environmental conditions, such as those found in extracellular solid tumor tissues, intracellular endosomes, and intracellular lysosomes, the conjugation of PPD may aid its selective delivery to these targets. Overall, results suggest that pH-dependent release of PPD, which expected in reduced cytotoxicity to non-targeted regions, may enhance the overall efficacy of PPD.
authors.affiliation: a Graduate School of Biotechnology and Ginseng Bank , College of Life Sciences, Kyung Hee University , Yongin-si, Gyeonggi-do , Republic of Korea.
authors.forename: Ramya
authors.initials: R
authors.lastname: Mathiyalagan
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Sathiyamoorthy
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.affiliation: b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: a Graduate School of Biotechnology and Ginseng Bank , College of Life Sciences, Kyung Hee University , Yongin-si, Gyeonggi-do , Republic of Korea.|b Deparment of Oriental Medicinal Biotechnology, College of Life Sciences , Kyung Hee University , Yongin-si , Gyeonggi-do , Republic of Korea.
authors.forename: Deok Chun
authors.initials: DC
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D036145:Ginsenosides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012502:Sapogenins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D036145:Ginsenosides; D012502:Sapogenins; D011092:Polyethylene Glycols; C062916:protopanaxadiol; C000595209:polyethylene glycol 1000
keywords: Cancer; ginsenosides; polyethylene glycol; protopanaxadiol; self-assembled nanoparticles; solubility