AAPS PharmSciTech

, 20:88 | Cite as

In Vitro Cytotoxicity and Bioavailability of Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin

  • Ajay Vijayakumar
  • Rengarajan Baskaran
  • Jeong-Heum BaekEmail author
  • Pasupathi Sundaramoorthy
  • Bong Kyu YooEmail author
Research Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery


Our aim was to investigate the cellular uptake, in vitro cytotoxicity and bioavailability of ginsenoside-modified nanostructured lipid carrier loaded with curcumin (G-NLC). The formulation was prepared by melt emulsification technique, in which water was added to the melted lipids and homogenized to give a uniform suspension of NLC (without ginsenoside) and G-NLC. Cellular uptake of curcumin in two colon cancer cell lines (HCT116 and HT29) was increased when administered using both NLC and G-NLC compared to control (curcumin dissolved into DMSO) as measured by fluorescence microscopy. Ginsenoside modification resulted in 2.0-fold and 1.4-fold increases in fluorescence intensity in HCT116 and HT29 cell lines, respectively, compared to plain NLC. In vitro cytotoxicity (assessed by MTT assay) had a dose-dependent relationship with curcumin concentration for both NLC and G-NLC. Although G-NLC was taken up more readily in HCT116 cells, ginsenoside modification did not produce a significant increase in cytotoxic effect; a significant increase was observed in HT29 cells. Oral administration of G-NLC in ten colon cancer patients produced an appreciable plasma level of unbound curcumin (2.9 ng/mL). In conclusion, introduction of ginsenoside into NLC enhanced the cellular uptake and cytotoxicity of curcumin as well as its oral bioavailability, and this strategy can be used to improve clinical outcomes in the treatment of colon cancer with similar genotype to HT29.


curcumin cellular uptake in vitro cytotoxicity ginsenoside modification colon cancer 



We thank Dr. Sung Won Park for his assistance with clinical study.

Funding Information

This study was supported by the Research Center Hospital Project of Gachon University Gil Medical Center (FRD2014-06-02).

Compliance with Ethical Standards

The study protocol was approved by the Institutional Review Board of Gachon University Gil Medical Center (GAIRB2015-87), and written informed consent was obtained from patients before their entry into the study.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Parsamanesh N, Moossavi M, Bahrami A, Butler AE, Sahebkar A. Therapeutic potential of curcumin in diabetic complications. Pharmacol Res. 2018;136:181–93.CrossRefGoogle Scholar
  2. 2.
    Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008;65:1631–52.CrossRefGoogle Scholar
  3. 3.
    Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011;10:1–19.CrossRefGoogle Scholar
  4. 4.
    Prasad S, Tyagi AK, Aggarwal BB. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat. 2014;46:2–18.CrossRefGoogle Scholar
  5. 5.
    Mahmood K, Zia KM, Zuber M, Salman M, Anjum MN. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: a review. Int J Biol Macromol. 2015;81:877–90.CrossRefGoogle Scholar
  6. 6.
    Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008;10:511–46.CrossRefGoogle Scholar
  7. 7.
    Epstein J, Sanderson IR, MacDonald TT. Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr. 2010;103:1545–57.CrossRefGoogle Scholar
  8. 8.
    Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res. 2014;58:516–27.CrossRefGoogle Scholar
  9. 9.
    Chaurasia S, Patel RR, Chaubey P, Kumar N, Khan G, Mishra B. Lipopolysaccharide based oral nanocarriers for the improvement of bioavailability and anticancer efficacy of curcumin. Carbohydr Polym. 2015;130:9–17.CrossRefGoogle Scholar
  10. 10.
    Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol. 2007;595:453–70.CrossRefGoogle Scholar
  11. 11.
    Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z, et al. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomark Prev. 2008;17:1411–7.CrossRefGoogle Scholar
  12. 12.
    Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64:353–6.CrossRefGoogle Scholar
  13. 13.
    Christensen LP. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2008;55:1–99.CrossRefGoogle Scholar
  14. 14.
    Leung KW, Wong AS. Pharmacology of ginsenosides: a literature review. Chin Med. 2010;5:20.CrossRefGoogle Scholar
  15. 15.
    Baskaran R, Madheswaran T, Sundaramoorthy P, Kim HM, Yoo BK. Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity. Int J Nanomedicine. 2014;9:3119–30.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Madheswaran T, Baskaran R, Sundaramoorthy P, Yoo BK. Enhanced skin permeation of 5α-reductase inhibitors entrapped into surface-modified liquid crystalline nanoparticles. Arch Pharm Res. 2015;38:534–42.CrossRefGoogle Scholar
  17. 17.
    Vijayakumar A, Baskaran R, Maeng HJ, Yoo BK. Ginsenoside improves physicochemical properties and bioavailability of curcumin-loaded nanostructured lipid carrier. Arch Pharm Res. 2017;40:864–74.CrossRefGoogle Scholar
  18. 18.
    Sundaramoorthy P, Baskaran R, Mishra SK, Jeong KY, Oh SH, Yoo BK, et al. Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells. Colloids Surf B: Biointerfaces. 2015;135:793–801.CrossRefGoogle Scholar
  19. 19.
    Safe S, Kasiappan R. Natural products as mechanism-based anticancer agents: sp transcription factors as targets. Phytother Res. 2016;30:1723–32.CrossRefGoogle Scholar
  20. 20.
    Singh S, Khar A. Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anti Cancer Agents Med Chem. 2006;6:259–70.CrossRefGoogle Scholar
  21. 21.
    Gianfredi V, Nucci D, Vannini S, Villarini M, Moretti M. In vitro biological effects of sulforaphane (SFN), epigallocatechin-3-gallate (EGCG), and curcumin on breast cancer cells: a systematic review of the literature. Nutr Cancer. 2017;69:969–78.CrossRefGoogle Scholar
  22. 22.
    Sa G, Das T. Anticancer effects of curcumin: cycle of life and death. Cell Div. 2008;3(1):14.CrossRefGoogle Scholar
  23. 23.
    Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11:495–510.CrossRefGoogle Scholar
  24. 24.
    Patil S, Choudhary B, Rathore A, Roy K, Mahadik K. Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells. Phytomedicine. 2015;22:1103–11.CrossRefGoogle Scholar
  25. 25.
    Ji H, Tang J, Li M, Ren J, Zheng N, Wu L. Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin. Drug Deliv. 2016;23:459–70.CrossRefGoogle Scholar
  26. 26.
    Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008;70:445–9.CrossRefGoogle Scholar
  27. 27.
    Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014;13:1–8.CrossRefGoogle Scholar
  28. 28.
    Sundaramoorthy P, Ramasamy T, Mishra SK, Jeong KY, Yong CS, Kim JO, et al. Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells. Acta Biomater. 2016;42:220–31.CrossRefGoogle Scholar
  29. 29.
    Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 2011;74:664–9.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Ajay Vijayakumar
    • 1
  • Rengarajan Baskaran
    • 2
  • Jeong-Heum Baek
    • 3
    Email author
  • Pasupathi Sundaramoorthy
    • 1
  • Bong Kyu Yoo
    • 1
    Email author
  1. 1.College of PharmacyGachon UniversityIncheonSouth Korea
  2. 2.Department of New Drug Development, College of MedicineInha UniversityIncheonSouth Korea
  3. 3.Division of Colon and Rectal Surgery, Department of Surgery, Gil Medical CenterGachon University College of MedicineIncheonSouth Korea

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