Characterization of ginsenoside compound K loaded ionically cross-linked carboxymethyl chitosan―calcium nanoparticles and its cytotoxic potential against prostate cancer cells

다국어 초록 (Multilingual Abstract)

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK―OCMC Nps), which enhance the aqueous solubility and stability of GK.
Methods: The GK―OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK―OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK―OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK―OCMC Nps.
Results: The GK―OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK―OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK―OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK―OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9.
Conclusion: GK―OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

목차 (Table of Contents)

• ABSTRACT
• 1. Introduction
• 2. Materials and methods
• 3. Results and discussion
• 4. Conclusion
• References

참고문헌 (Reference)

1 Zhang Y, "pH-and voltage-responsive chitosan hydrogel through covalent cross-linking with catechol" 116 (116): 1579-1585, 2012

2 Luesakul U, "pH-Responsive Selenium nanoparticles stabilized by folate-chitosan delivering doxorubicin for overcoming drug-resistant Cancer Cells" 181 : 841-850, 2017

3 Eunji Kim, "The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng" 고려인삼학회 42 (42): 218-224, 2018

4 Kalliola S, "The pH sensitive properties of carboxymethyl chitosan nanoparticles cross-linked with calcium ions" 153 : 229-236, 2017

5 Wurstle ML, "The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome" 318 (318): 1213-1220, 2012

6 Yang L, "Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer" 12 : 7653-7667, 2017

7 Sang Yeol Lee, "Synergistic effect of maclurin on ginsenoside compound K induced inhibition of the transcriptional expression of matrix metalloproteinase-1 in HaCaT human keratinocyte cells" 고려인삼학회 42 (42): 229-232, 2018

8 Shi Y, "Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide" 161 : 67-72, 2018

9 Berger J, "Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications" 57 (57): 19-34, 2004

10 Badran MM, "Preparation and characterization of polymeric nanoparticles surface modified with chitosan for target treatment of colorectal cancer" 95 : 643-649, 2017

11 Wu J, "Preparation and biological activity studies of resveratrol loaded ionically cross-linked chitosan-TPP nanoparticles" 175 : 170-177, 2017

12 Baek J, "Phosphorylated-CNC/modifiedchitosan nanocomplexes for the stabilization of Pickering emulsions" 206 : 520-527, 2019

13 Lu W, "Peroxiredoxin 2 is upregulated in colorectal cancer and contributes to colorectal cancer cells’ survival by protecting cells from oxidative stress" 2014

14 Hou J, "Octyl ester of ginsenoside compound K as novel anti-hepatoma compound : synthesis and evaluation on murine H22 cells in vitro and in vivo" 91 (91): 951-956, 2018

15 Huang YC, "O-carboxymethyl chitosan/fucoidan nanoparticles increase cellular curcumin uptake" 53 : 261-269, 2016

16 de la Puente P, "Nanoparticle delivery systems, general approaches, and their implementation in multiple myeloma" 98 (98): 529-541, 2017

17 Hasegawa H, "Main ginseng saponin metabolites formed by intestinal bacteria" 62 (62): 453-457, 1996

18 Li Y, "Ginsenoside metabolite compound K enhances the efficacy of cisplatin in lung cancer cells" 7 (7): 400-406, 2015

19 Wei S, "Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5’monophosphate kinase : a study in vitro and in vivo" 139 : 8-15, 2015

20 Attele AS, "Ginseng pharmacology : multiple constituents and multiple actions" 58 (58): 1685-1693, 1999

21 Dramou P, "Folic acid-conjugated chitosan oligosaccharide-magnetic halloysite nanotubes as a delivery system for camptothecin" 197 : 117-127, 2018

22 Jain A, "Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles" 137 : 65-74, 2016

23 Subhapradha N, "Fabrication of beta-chitosan nanoparticles and its anticancer potential against human hepatoma cells" 94 (94): 194-201, 2017

24 Yadav P, "Enhancement of anticancer activity and drug delivery of chitosan-curcumin nanoparticle via molecular docking and simulation analysis" 182 : 188-198, 2018

25 Anitha A, "Efficient water soluble O-carboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells" 83 (83): 452-461, 2011

26 Maya S, "Efficacy of tetracycline encapsulated O-carboxymethyl chitosan nanoparticles against intracellular infections of Staphylococcus aureus" 51 (51): 392-399, 2012

27 Yu H, "Development of liposomal Ginsenoside Rg3 : formulation optimization and evaluation of its anticancer effects" 2013

28 Zhang Z, "Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy : in vitro and in vivo evaluations" 25 (25): 166-177, 2018

29 Lu G, "Degradation of covalently cross-linked carboxymethyl chitosan and its potential application for peripheral nerve regeneration" 43 (43): 3807-3818, 2007

30 Muddineti OS, "Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery" 14 (14): 715-726, 2017

31 Mary Lazer L, "Chitosan-based nanoformulation enhances the anticancer efficacy of hesperetin" 107 (107): 1988-1998, 2018

32 Khan MA, "Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies" 97 : 115-122, 2017

33 Singh P, "Bovine serum albumin as a nanocarrier for the efficient delivery of ginsenoside compound K : preparation, physicochemical characterizations and in vitro biological studies" 7 (7): 15397-15407, 2017

34 Jayakumar R, "Biomedical applications of chitin and chitosan based nanomaterialsda short review" 82 (82): 227-232, 2010

35 Zhang Y, "Ascorbyl palmitate/dalpha-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo" 12 : 605-614, 2017

36 Zuly Elizabeth Jiménez-Pérez, "Applications of Panax ginseng leaves-mediated gold nanoparticles in cosmetics relation to antioxidant, moisture retention, and whitening effect on B16BL6 cells" 고려인삼학회 42 (42): 327-333, 2018

37 Hu W, "Apigenin-7-O-b-D-glucuronide inhibits LPS-induced inflammation through the inactivation of AP-1 and MAPK signaling pathways in RAW 264.7 macrophages and protects mice against endotoxin shock" 7 (7): 1002-1013, 2016

38 Shin-Jung Kim, "Anti-breast cancer activity of Fine Black ginseng (Panax ginseng Meyer) and ginsenoside Rg5" 고려인삼학회 39 (39): 125-134, 2015

39 Patel S, "Adaptogenic herb ginseng(Panax)as medical food : status quo and future prospects" 85 : 120-127, 2017

40 Singh PK, "1, 3 b-Glucan anchored, paclitaxel loaded chitosan nanocarrier endows enhanced hemocompatibility with efficient anti-glioblastoma stem cells therapy" 180 : 365-375, 2017