Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside


The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200 nm, and polydispersity index was in the range of 0.101–0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or recrystallization of curcumin even at 10,000 μg/ml concentration as NLC-PG in distilled water, indicating significantly enhanced solubility. TEM image showed that the nanoparticles were monodispersed with a multilayered core/shell structure. X-ray diffraction and FTIR spectroscopy showed that curcumin was amorphous in the NLC-PG, and there was no interaction between curcumin and the excipients. In vitro release study using simulated gastric/intestinal fluid media revealed that the release rate (Jss) of curcumin from the NLC-PG increased as a function of the ginsenoside content in the lipid carrier. Moreover, the Jss of curcumin kept gradually increasing in the presence of lipase, whereas in the presence of viscozyme, it sharply increased until the ginsenoside content reached 9.09% and subsequently plateaued. Partially hydrolyzed ginsenoside increased the Jss of curcumin from curcumin-loaded NLC-PG and therefore may be useful for improving the bioavailability of curcumin.

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  1. 1.

    de Almeida M, da Rocha BA, Francisco CRL, Miranda CG, Santos PDF, de Araujo PHH, et al. Evaluation of the in vivo acute antiinflammatory response of curcumin-loaded nanoparticles. Food Funct. 2018;24:440–9.

    Article  Google Scholar 

  2. 2.

    Waly MI, Al-Bulushi IM, Al-Hinai S, Guizani N, Al-Malki RN, Rahman MS. The protective effect of curcumin against nitrosamine-induced gastric oxidative stress in rats. Prev Nutr Food Sci. 2018;23:288–93.

    CAS  Article  Google Scholar 

  3. 3.

    Choi YH, Han DH, Kim SW, Kim MJ, Sung HH, Jeon HG, et al. A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation. Prostate. 2019;79:614–21.

    CAS  Article  Google Scholar 

  4. 4.

    Tajbakhsh A, Hasanzadeh M, Rezaee M, Khedri M, Khazaei M, ShahidSales S, et al. Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways. J Cell Physiol. 2018;233:2183–92.

    CAS  Article  Google Scholar 

  5. 5.

    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.

    CAS  Article  Google Scholar 

  6. 6.

    Asai A, Miyazawa T. Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci. 2000;67:2785–93.

    CAS  Article  Google Scholar 

  7. 7.

    Berginc K, Trontelj J, Basnet NS, Kristl A. Physiological barriers to the oral delivery of curcumin. Pharmazie. 2012;67:518–24.

    CAS  PubMed  Google Scholar 

  8. 8.

    Kunihiro AG, Brickey JA, Frye JB, Luis PB, Schneider C, Funk JL. Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone metastatic breast cancer cells and is enriched in bone compared to other tissues. J Nutr Biochem. 2019;63:150–6.

    CAS  Article  Google Scholar 

  9. 9.

    Mourtas S, Lazar AN, Markoutsa E, Duyckaerts C, Antimisiaris SG. Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease. Eur J Med Chem. 2014;80:175–83.

    CAS  Article  Google Scholar 

  10. 10.

    Lin YH, Lin JH, Hong YS. Development of chitosan/poly-γ-glutamic acid/pluronic/curcumin nanoparticles in chitosan dressings for wound regeneration. J Biomed Mater Res B Appl Biomater. 2017;105:81–90.

    CAS  Article  Google Scholar 

  11. 11.

    Popat A, Karmakar S, Jambhrunkar S, Xu C, Yu C. Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity. Colloids Surf B Biointerfaces. 2014;117:520–7.

    CAS  Article  Google Scholar 

  12. 12.

    Udompornmongkol P, Chiang BH. Curcumin-loaded polymeric nanoparticles for enhanced anti-colorectal cancer applications. J Biomater Appl. 2015;30:537–46.

    CAS  Article  Google Scholar 

  13. 13.

    Tabatabaei Mirakabad FS, Akbarzadeh A, Milani M, Zarghami N, Taheri-Anganeh M, Zeighamian V, et al. A comparison between the cytotoxic effects of pure curcumin and curcumin-loaded PLGA-PEG nanoparticles on the MCF-7 human breast cancer cell line. Artif Cells Nanomed Biotechnol. 2016;44:423–30.

    CAS  Article  Google Scholar 

  14. 14.

    Guo F, Wu J, Wu W, Huang D, Yan Q, Yang Q, et al. PEGylated self-assembled enzyme-responsive nanoparticles for effective targeted therapy against lung tumors. J Nanobiotechnology. 2018;16:57.

    CAS  Article  Google Scholar 

  15. 15.

    Guo F, Guo D, Zhang W, Yan Q, Yang Y, Hong W, et al. Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology. Eur J Pharm Sci. 2017;99:328–36.

    CAS  Article  Google Scholar 

  16. 16.

    Szymusiak M, Hu X, Leon Plata PA, Ciupinski P, Wang ZJ, Liu Y. Bioavailability of curcumin and curcumin glucuronide in the central nervous system of mice after oral delivery of nano-curcumin. Int J Pharm. 2016;511:415–23.

    CAS  Article  Google Scholar 

  17. 17.

    Zheng B, Peng S, Zhang X, McClements DJ. Impact of delivery system type on curcumin bioaccessibility: comparison of curcumin-loaded nanoemulsions with commercial curcumin supplements. J Agric Food Chem. 2018;66:10816–26.

    CAS  Article  Google Scholar 

  18. 18.

    Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010;58:2095–9.

    CAS  Article  Google Scholar 

  19. 19.

    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.

    CAS  Article  Google Scholar 

  20. 20.

    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.

    CAS  Article  Google Scholar 

  21. 21.

    Vijayakumar A, Baskaran R, Baek JH, Sundaramoorthy P, Yoo BK. In vitro cytotoxicity and bioavailability of ginsenoside-modified nanostructured lipid carrier containing curcumin. AAPS PharmSciTech. 2019;20:88.

    Article  Google Scholar 

  22. 22.

    Clayton KN, Salameh JW, Wereley ST, Kinzer-Ursem TL. Physical characterization of nanoparticle size and surface modification using particle scattering diffusometry. Biomicrofluidics. 2016;10:054107.

    Article  Google Scholar 

  23. 23.

    Chen J, Qin X, Zhong S, Chen S, Su W, Liu Y. Characterization of curcumin/cyclodextrin polymer inclusion complex and investigation on its antioxidant and antiproliferative activities. Molecules. 2018;23:1179.

    Article  Google Scholar 

  24. 24.

    Davis BM, Pahlitzsch M, Guo L, Balendra S, Shah P, Ravindran N, et al. Topical curcumin nanocarriers are neuroprotective in eye disease. Sci Rep. 2018;8:11066.

    Article  Google Scholar 

  25. 25.

    Cheng KK, Chan PS, Fan S, Kwan SM, Yeung KL, Wang YX, et al. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI). Biomaterials. 2015;44:155–72.

    CAS  Article  Google Scholar 

  26. 26.

    Chen X, Zou LQ, Niu J, Liu W, Peng SF, Liu CM. The stability, sustained release and cellular antioxidant activity of curcumin nanoliposomes. Molecules. 2015;20:14293–311.

    CAS  Article  Google Scholar 

  27. 27.

    Wan S, Sun Y, Qi X, Tan F. Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech. 2012;13:159–66.

    CAS  Article  Google Scholar 

  28. 28.

    Mohan PR, Sreelakshmi G, Muraleedharan CV, Joseph R. Water soluble complexes of curcumin with cyclodextrins: characterization by FT-Raman spectroscopy. Vib Spectrosc. 2012;62:77–84.

    CAS  Article  Google Scholar 

  29. 29.

    Hu L, Shi Y, Li JH, Gao N, Ji J, Niu F, et al. Enhancement of oral bioavailability of curcumin by a novel solid dispersion system. AAPS PharmSciTech. 2015;16:1327–34.

    CAS  Article  Google Scholar 

  30. 30.

    Jeevana Jyothi B, Sravani R. Development of curcumin nanocrystals and evaluation of GI absorption efficiency in comparison with curcumin and turmeric powder. World J Pharm Pharm Sci. 2016;5:1990–2003.

    Google Scholar 

  31. 31.

    Song BK, Kim KM, Choi KD, Im WT. Production of the rare ginsenoside Rh2-mix (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by enzymatic conversion combined with acid treatment and evaluation of its anti-cancer activity. J Microbiol Biotechnol. 2017;27:1233–41.

    CAS  Article  Google Scholar 

  32. 32.

    Choi HS, Kim SY, Park Y, Jung EY, Suh HJ. Enzymatic transformation of ginsenosides in Korean red ginseng (Panax ginseng Meyer) extract prepared by Spezyme and Optidex. J Ginseng Res. 2014;38:264–9.

    CAS  Article  Google Scholar 

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The authors would like to thank Ms. Sun Kyung Choi for her assistance with the in vitro release experiments and manuscript documentations.

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Correspondence to Bong-Kyu Yoo.

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Selvaraj, K., Yoo, B. Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside. AAPS PharmSciTech 20, 252 (2019).

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  • curcumin
  • nanostructured lipid carrier
  • partially hydrolyzed ginsenoside
  • in vitro release