AAPS PharmSciTech

, 20:145 | Cite as

Preparation, Characterization, and In vitro Evaluation of Curcumin- and Resveratrol-Loaded Solid Lipid Nanoparticles

  • Ashwini Gumireddy
  • Ryann Christman
  • Dunesh Kumari
  • Amit Tiwari
  • E. Jeffrey North
  • Harsh ChauhanEmail author
Research Article Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems
Part of the following topical collections:
  1. Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems


Curcumin and resveratrol are natural compounds with significant anticancer activity; however, their bioavailability is limited due to poor solubility. This study aimed to overcome the solubility problem by means of solid lipid nanoparticles (SLN). 2-Hydroxypropyl β-cyclodextrin (HPβCD) was selected from a range of polymers based on miscibility and molecular interactions. SLNs were obtained by probe sonication and freeze-drying curcumin-resveratrol with/without HPβCD incorporated in gelucire 50/13. SLNs were characterized by dynamic light scattering (DLS), zeta potential, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and physical stability. The in vitro release of drugs from the SLNs was performed by the direct dispersion method and analyzed using a validated UV-visible method. In vitro efficacy was tested using a colorectal cancer cell line. Curcumin-resveratrol-gelucire 50/13-HPβCD (CRG-CD) and curcumin-resveratrol-gelucire 50/13(CRG) SLNs showed a particle size from 100 to 150 nm and were not in the crystalline state per PXRD results. MDSC results complimented PXRD results by the absence of melting endotherm of curcumin; TGA showed no weight loss, confirming the absence of organic solvent residual, and the shape of the SLNs was confirmed as spherical by SEM. CRG SLNs were stable for 21 days with respect to particle size and zeta potential. MTT assay indicated better IC50 value for CRG as compared to CRG-CD. Hence, novel SLNs of curcumin and resveratrol incorporated in gelucire 50/13 and HPβCD were prepared and characterized to improve their bioavailability and anticancer activity.


curcumin resveratrol solid lipid nanoparticles 2-hydroxypropyl β-cyclodextrin anticancer 



  1. 1.
    Odoux C, Fohrer H, Hoppo T, Guzik L, Stolz DB, Lewis DW, et al. A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Res. 2008;68(17):6932–41.PubMedPubMedCentralGoogle Scholar
  2. 2.
    team TACSmaec. Key statistics for colorectal cancer 2018 [updated 20180221. Available from:
  3. 3.
    Arnold M, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–91.PubMedGoogle Scholar
  4. 4.
    Kronawitter U, Kemeny NE, Blumgart L. Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course after treatment with 5-fluorouracil and leucovorin—a case report. Cancer. 1997;80(4):656–60.PubMedGoogle Scholar
  5. 5.
    Dikken C, Sitzia J. Patients' experiences of chemotherapy: side-effects associated with 5-fluorouracil + folinic acid in the treatment of colorectal cancer. J Clin Nurs. 1998;7(4):371–9.PubMedGoogle Scholar
  6. 6.
    Zhang B, Fang C, Deng D, Xia L. Research progress on common adverse events caused by targeted therapy for colorectal cancer. Oncol Lett. 2018;16(1):27–33.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Aras A, Khokhar AR, Qureshi MZ, Silva MF, Sobczak-Kupiec A, Pineda EA, et al. Targeting cancer with nano-bullets: curcumin, EGCG, resveratrol and quercetin on flying carpets. Asian Pac J Cancer Prev. 2014;15(9):3865–71.PubMedGoogle Scholar
  8. 8.
    Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm. 2010;343(9):489–99.Google Scholar
  9. 9.
    Villegas I, Sanchez-Fidalgo S, Alarcon de la Lastra C. New mechanisms and therapeutic potential of curcumin for colorectal cancer. Mol Nutr Food Res. 2008;52(9):1040–61.PubMedGoogle Scholar
  10. 10.
    Carter LG, D’Orazio JA, Pearson KJ. Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer. 2014;21(3):R209–25.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Majumdar AP, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, et al. Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer. 2009;61(4):544–53.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm. 2011;420(1):1–10.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Bhatt P, Lalani R, Mashru R, Misra A. Anti-FSHR antibody Fab’fragment conjugated immunoliposomes loaded with cyclodextrin-paclitaxel complex for improved in vitro efficacy on ovarian cancer cells: AACR. Cancer Res 2016;76(14 Suppl):Abstract nr 2065.Google Scholar
  14. 14.
    De Leo V, Milano F, Mancini E, Comparelli R, Giotta L, Nacci A, et al. Encapsulation of curcumin-loaded liposomes for colonic drug delivery in a pH-responsive polymer cluster using a pH-driven and organic solvent-free process. Molecules (Basel, Switzerland). 2018;23(4). Scholar
  15. 15.
    Patel J, Amrutiya J, Bhatt P, Javia A, Jain M, Misra A. Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells. J Microencapsul. 2018;35(2):204–17.PubMedGoogle Scholar
  16. 16.
    Yewale C, Baradia D, Patil S, Bhatt P, Amrutiya J, Gandhi R, et al. Docetaxel loaded immunonanoparticles delivery in EGFR overexpressed breast carcinoma cells. J Drug Deliv Sci Technol. 2018;45:334–45.Google Scholar
  17. 17.
    Wang Y, Wang C, Zhao J, Ding Y, Li L. A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability. J Colloid Interface Sci. 2017;485:91–8.PubMedGoogle Scholar
  18. 18.
    Chang CW, Wong CY, Wu YT, Hsu MC. Development of a solid dispersion system for improving the oral bioavailability of resveratrol in rats. Eur J Drug Metab Pharmacokinet. 2017;42(2):239–49.PubMedGoogle Scholar
  19. 19.
    Chuah AM, Jacob B, Jie Z, Ramesh S, Mandal S, Puthan JK, et al. Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin. Food Chem. 2014;156:227–33.PubMedGoogle Scholar
  20. 20.
    Saralkar P, Dash AK. Alginate nanoparticles containing curcumin and resveratrol: preparation, characterization, and in vitro evaluation against DU145 prostate cancer cell line. AAPS PharmSciTech. 2017;18(7):2814–23.PubMedGoogle Scholar
  21. 21.
    Neves AR, Lucio M, Martins S, Lima JL, Reis S. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability. Int J Nanomedicine. 2013;8:177–87.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Vhora I, Patil S, Bhatt P, Gandhi R, Baradia D, Misra A. Receptor-targeted drug delivery: current perspective and challenges. Ther Deliv. 2014;5(9):1007–24.PubMedGoogle Scholar
  23. 23.
    Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349–58.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Müller RH, Runge S, Ravelli V, Mehnert W, Thünemann AF, Souto EB. Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN®) versus drug nanocrystals. Int J Pharm. 2006;317(1):82–9.PubMedGoogle Scholar
  25. 25.
    zur Muhlen A, Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery—drug release and release mechanism. Eur J Pharm Biopharm. 1998;45(2):149–55.PubMedGoogle Scholar
  26. 26.
    Yang R, Gao R, Li F, He H, Tang X. The influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process. Drug Dev Ind Pharm. 2011;37(2):139–48.PubMedGoogle Scholar
  27. 27.
    Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73(2–3):121–36.PubMedGoogle Scholar
  28. 28.
    Li L, Braiteh FS, Kurzrock R. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer. 2005;104(6):1322–31.PubMedGoogle Scholar
  29. 29.
    Kumar S, Kesharwani SS, Mathur H, Tyagi M, Bhat GJ, Tummala H. Molecular complexation of curcumin with pH sensitive cationic copolymer enhances the aqueous solubility, stability and bioavailability of curcumin. Eur J Pharm Sci. 2016;82:86–96.PubMedGoogle Scholar
  30. 30.
    Falconieri MC, Adamo M, Monasterolo C, Bergonzi MC, Coronnello M, Bilia AR. New dendrimer-based nanoparticles enhance curcumin solubility. Planta Med. 2017;83(5):420–5.PubMedGoogle Scholar
  31. 31.
    Pawar H, Surapaneni SK, Tikoo K, Singh C, Burman R, Gill MS, et al. Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: in vitro evaluation, pharmacokinetic and biodistribution in rats. Drug Deliv. 2016;23(4):1453–68.PubMedGoogle Scholar
  32. 32.
    Swaminathan S, Cavalli R, Trotta F. Cyclodextrin-based nanosponges: a versatile platform for cancer nanotherapeutics development. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016;8(4):579–601.PubMedGoogle Scholar
  33. 33.
    Kumar A, Kaur G, Kansal SK, Chaudhary GR, Mehta SK. Enhanced solubilization of curcumin in mixed surfactant vesicles. Food Chem. 2016;199:660–6.PubMedGoogle Scholar
  34. 34.
    Li M, Gao M, Fu Y, Chen C, Meng X, Fan A, et al. Acetal-linked polymeric prodrug micelles for enhanced curcumin delivery. Colloids Surf B: Biointerfaces. 2016;140:11–8.PubMedGoogle Scholar
  35. 35.
    Jannin V, Chevrier S, Michenaud M, Dumont C, Belotti S, Chavant Y, et al. Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity. Int J Pharm. 2015;495(1):385–92.PubMedGoogle Scholar
  36. 36.
    Aditya NP, Yang H, Kim S, Ko S. Fabrication of amorphous curcumin nanosuspensions using beta-lactoglobulin to enhance solubility, stability, and bioavailability. Colloids Surf B: Biointerfaces. 2015;127:114–21.PubMedGoogle Scholar
  37. 37.
    Liu R, Sun L, Fang S, Wang S, Chen J, Xiao X, et al. Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin: development, characterization, in vitro permeation and in vivo pharmacokinetic studies. Pharm Dev Technol. 2016;21(5):576–82.PubMedGoogle Scholar
  38. 38.
    Duan Y, Cai X, Du H, Zhai G. Novel in situ gel systems based on P123/TPGS mixed micelles and gellan gum for ophthalmic delivery of curcumin. Colloids Surf B: Biointerfaces. 2015;128:322–30.PubMedGoogle Scholar
  39. 39.
    Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit(R) E PO solid dispersion: a simple and potent method to solve the problems of curcumin. Eur J Pharm Biopharm. 2015;94:322–32.PubMedGoogle Scholar
  40. 40.
    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(1):159–66.PubMedGoogle Scholar
  41. 41.
    Chowdhury N, Vhora I, Patel K, Bagde A, Kutlehria S, Singh M. Development of hot melt extruded solid dispersion of tamoxifen citrate and resveratrol for synergistic effects on breast cancer cells. AAPS PharmSciTech. 2018;19:3287–97.PubMedGoogle Scholar
  42. 42.
    Zhang L, Zhu W, Yang C, Guo H, Yu A, Ji J, et al. A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting. Int J Nanomedicine. 2012;7:151–62.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Jaisamut P, Wiwattanawongsa K, Wiwattanapatapee R. A novel self-microemulsifying system for the simultaneous delivery and enhanced oral absorption of curcumin and resveratrol. Planta Med. 2017;83(5):461–7.PubMedGoogle Scholar
  44. 44.
    Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63(3):170–83.PubMedGoogle Scholar
  45. 45.
    Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine. 2010;6(1):153–60.PubMedGoogle Scholar
  46. 46.
    Jayaprakasha GK, Chidambara Murthy KN, Patil BS. Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein. Eur J Pharmacol. 2016;789:291–300.PubMedGoogle Scholar
  47. 47.
    Marcato PD, Duran N. New aspects of nanopharmaceutical delivery systems. J Nanosci Nanotechnol. 2008;8(5):2216–29.PubMedGoogle Scholar
  48. 48.
    Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2):165–96.PubMedGoogle Scholar
  49. 49.
    Wang P, Zhang L, Peng H, Li Y, Xiong J, Xu Z. The formulation and delivery of curcumin with solid lipid nanoparticles for the treatment of on non-small cell lung cancer both in vitro and in vivo. Mater Sci Eng C. 2013;33(8):4802–8.Google Scholar
  50. 50.
    Zhu R, Wu X, Xiao Y, Gao B, Xie Q, Liu H, et al. Synergetic effect of SLN-curcumin and LDH-5-Fu on SMMC-7721 liver cancer cell line. Cancer Biother Radiopharm. 2013;28(8):579–87.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Jose S, Anju SS, Cinu TA, Aleykutty NA, Thomas S, Souto EB. In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery. Int J Pharm. 2014;474(1–2):6–13.PubMedGoogle Scholar
  52. 52.
    Marcolino VA, Zanin GM, Durrant LR, Benassi Mde T, Matioli G. Interaction of curcumin and bixin with beta-cyclodextrin: complexation methods, stability, and applications in food. J Agric Food Chem. 2011;59(7):3348–57.PubMedGoogle Scholar
  53. 53.
    Jahed V, Zarrabi A, Bordbar AK, Hafezi MS. NMR ((1)H, ROESY) spectroscopic and molecular modelling investigations of supramolecular complex of beta-cyclodextrin and curcumin. Food Chem. 2014;165:241–6.PubMedGoogle Scholar
  54. 54.
    Hanaor D, Michelazzi M, Leonelli C, Sorrell CC. The effects of carboxylic acids on the aqueous dispersion and electrophoretic deposition of ZrO2. J Eur Ceram Soc. 2012;32(1):235–44.Google Scholar
  55. 55.
    nanoComposix. Zeta potential nanoparticle analysis. Available from:
  56. 56.
    Ayan AK, Yenilmez A, Eroglu H. Evaluation of radiolabeled curcumin-loaded solid lipid nanoparticles usage as an imaging agent in liver-spleen scintigraphy. Mater Sci Eng C. 2017;75:663–70.Google Scholar
  57. 57.
    Meng F, Trivino A, Prasad D, Chauhan H. Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions. Eur J Pharm Sci. 2015;71:12–24.PubMedGoogle Scholar
  58. 58.
    Coradini K, Lima FO, Oliveira CM, Chaves PS, Athayde ML, Carvalho LM, et al. Co-encapsulation of resveratrol and curcumin in lipid-core nanocapsules improves their in vitro antioxidant effects. Eur J Pharm Biopharm. 2014;88(1):178–85.PubMedGoogle Scholar
  59. 59.
    Friedrich RB, Kann B, Coradini K, Offerhaus HL, Beck RC, Windbergs M. Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin. Eur J Pharm Sci. 2015;78:204–13.PubMedGoogle Scholar
  60. 60.
    Guo C, Yin J, Chen D. Co-encapsulation of curcumin and resveratrol into novel nutraceutical hyalurosomes nano-food delivery system based on oligo-hyaluronic acid-curcumin polymer. Carbohydr Polym. 2018;181:1033–7.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Ashwini Gumireddy
    • 1
  • Ryann Christman
    • 2
  • Dunesh Kumari
    • 3
  • Amit Tiwari
    • 2
  • E. Jeffrey North
    • 4
  • Harsh Chauhan
    • 4
    Email author
  1. 1.Department of Pharmaceutical sciencesDuquesne UniversityPittsburghUSA
  2. 2.Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical SciencesUniversity of ToledoToledoUSA
  3. 3.Chemistry DepartmentCollege of Saint MaryOmahaUSA
  4. 4.Department of Pharmacy Sciences, School of Pharmacy and Health ProfessionsCreighton UniversityOmahaUSA

Personalised recommendations