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Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability

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Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

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  1. Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv. 2014;32(6):1053–64.

    Article  PubMed  CAS  Google Scholar 

  2. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787–809.

    Article  PubMed  CAS  Google Scholar 

  3. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.

    Article  PubMed  CAS  Google Scholar 

  4. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495–510.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol. 2006;545(1):51–64.

    Article  PubMed  CAS  Google Scholar 

  6. Thangapazham RL, Sharma A, Maheshwari RK. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006;8(3):E443–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005;2(2):131–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195–218.

    Article  PubMed  CAS  Google Scholar 

  9. Wahlang B, Pawar YB, Bansal AK. Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur J Pharm Biopharm. 2011;77(2):275–82.

    Article  PubMed  CAS  Google Scholar 

  10. Song Z, Feng R, Sun M, Guo C, Gao Y, Li L, et al. Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: preparation, pharmacokinetics and distribution in vivo. J Colloid Interface Sci. 2011;354(1):116–23.

    Article  PubMed  CAS  Google Scholar 

  11. Tomren MA, Masson M, Loftsson T, Tonnesen HH. Studies on curcumin and curcuminoids XXXI. Symmetric and asymmetric curcuminoids: stability, activity and complexation with cyclodextrin. Int J Pharm. 2007;338(1–2):27–34.

    Article  PubMed  CAS  Google Scholar 

  12. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18.

    Article  PubMed  CAS  Google Scholar 

  13. 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(1):2–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Paradkar A, Ambike AA, Jadhav BK, Mahadik KR. Characterization of curcumin-PVP solid dispersion obtained by spray drying. Int J Pharm. 2004;271(1–2):281–6.

    Article  PubMed  CAS  Google Scholar 

  16. Onoue S, Suzuki H, Kojo Y, Matsunaga S, Sato H, Mizumoto T, et al. Self-micellizing solid dispersion of cyclosporine A with improved dissolution and oral bioavailability. Eur J Pharm Sci. 2014;62:16–22.

    Article  PubMed  CAS  Google Scholar 

  17. Mendonca LM, Machado Cda S, Teixeira CC, Freitas LA, Bianchi ML, Antunes LM. Comparative study of curcumin and curcumin formulated in a solid dispersion: evaluation of their antigenotoxic effects. Genet Mol Biol. 2015;38(4):490–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Vo CL, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm. 2013;85(3 Pt B):799–813.

    Article  PubMed  CAS  Google Scholar 

  19. Singh A, Van den Mooter G. Spray drying formulation of amorphous solid dispersions. Adv Drug Deliv Rev. 2016;100:27–50.

    Article  PubMed  CAS  Google Scholar 

  20. Lee JY, Kang WS, Piao J, Yoon IS, Kim DD, Cho HJ. Soluplus(R)/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan. Drug Des Devel Ther. 2015;9:2745–56.

    PubMed  PubMed Central  Google Scholar 

  21. Lian X, Dong J, Zhang J, Teng Y, Lin Q, Fu Y, et al. Soluplus((R)) based 9-nitrocamptothecin solid dispersion for peroral administration: preparation, characterization, in vitro and in vivo evaluation. Int J Pharm. 2014;477(1–2):399–407.

    Article  PubMed  CAS  Google Scholar 

  22. Teixeira CC, Mendonca LM, Bergamaschi MM, Queiroz RH, Souza GE, Antunes LM, et al. Microparticles containing curcumin solid dispersion: stability, bioavailability and anti-inflammatory activity. AAPS PharmSciTech. 2016;17(2):252–61.

    Article  PubMed  CAS  Google Scholar 

  23. Song IS, Cha JS, Choi MK. Characterization, in vivo and in vitro evaluation of solid dispersion of curcumin containing d-alpha-tocopheryl polyethylene glycol 1000 succinate and mannitol. Molecules. 2016;21(10)

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. Parikh A, Kathawala K, Tan CC, Garg S, Zhou XF Self-nanomicellizing solid dispersion of Edaravone: part I oral bioavailability improvement drug design, development and therapy 2018.

  26. Liu J, Zou M, Piao H, Liu Y, Tang B, Gao Y, et al. Characterization and pharmacokinetic study of aprepitant solid dispersions with Soluplus(R). Molecules. 2015;20(6):11345–56.

    Article  PubMed  CAS  Google Scholar 

  27. Wegmann M, Parola L, Bertera FM, Taira CA, Cagel M, Buontempo F, Bernabeu E, Hocht C, Chiappetta DA, Moretton MA. Novel carvedilol paediatric nanomicelle formulation: in-vitro characterization and in-vivo evaluation, J Pharm Pharmacol 2016.

  28. Dian L, Yu E, Chen X, Wen X, Zhang Z, Qin L, et al. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res Lett. 2014;9(1):2406.

    Article  PubMed  CAS  Google Scholar 

  29. Lim SM, Pang ZW, Tan HY, Shaikh M, Adinarayana G, Garg S. Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. Drug Dev Ind Pharm. 2015;41(11):1847–55.

    Article  PubMed  CAS  Google Scholar 

  30. Wang LL, He DD, Wang SX, Dai YH, Ju JM, Zhao CL. Preparation and evaluation of curcumin-loaded self-assembled micelles. Drug Dev Ind Pharm. 2017:1–7.

  31. Wang J, Wang L, Zhang L, He D, Ju J, Li W Studies on the curcumin phospholipid complex solidified with Soluplus((R)), J Pharm Pharmacol 2017.

  32. Li M, Xin M, Guo C, Lin G, Wu X. New nanomicelle curcumin formulation for ocular delivery: improved stability, solubility, and ocular anti-inflammatory treatment. Drug Dev Ind Pharm. 2017;43(11):1846–57.

    Article  PubMed  CAS  Google Scholar 

  33. Mande PP, Bachhav SS, Devarajan PV. Solid dispersion of curcumin as polymeric films for bioenhancement and improved therapy of rheumatoid arthritis. Pharm Res. 2016;33(8):1972–87.

    Article  PubMed  CAS  Google Scholar 

  34. Alshahrani SM, Lu W, Park JB, Morott JT, Alsulays BB, Majumdar S, et al. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus(R) and HPMCAS-HF. AAPS PharmSciTech. 2015;16(4):824–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Parikh A, Kathawala K, Tan CC, Garg S, Zhou XF. Development of a novel oral delivery system of edaravone for enhancing bioavailability. Int J Pharm. 2016;515(1–2):490–500.

    Article  PubMed  CAS  Google Scholar 

  36. Parikh A, Kathawala K, Tan CC, Garg S, Zhou XF. Lipid-based nanosystem of edaravone: development, optimization, characterization and in vitro/in vivo evaluation. Drug Delivery. 2017;24(1):962–78.

    Article  PubMed  CAS  Google Scholar 

  37. Seo SW, Han HK, Chun MK, Choi HK. Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol(R) HS15 as a carrier. Int J Pharm. 2012;424(1–2):18–25.

    Article  PubMed  CAS  Google Scholar 

  38. Kyaw Oo M, Mandal UK, Chatterjee B. Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design. Pharm Dev Technol. 2015:1–11.

  39. Wang W, Song Y, Petrovski K, Eats P, Trott DJ, Wong HS, et al. Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle. Drug Des Devel Ther. 2015;9:631–42.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Homayouni A, Sadeghi F, Nokhodchi A, Varshosaz J, Afrasiabi Garekani H. Preparation and characterization of celecoxib dispersions in soluplus((R)): comparison of spray drying and conventional methods. Iranian J Pharm Res: IJPR. 2015;14(1):35–50.

    CAS  Google Scholar 

  41. Cerpnjak K, Zvonar A, Vrecer F, Gasperlin M. Characterization of naproxen-loaded solid SMEDDSs prepared by spray drying: the effect of the polysaccharide carrier and naproxen concentration. Int J Pharm. 2015;485(1–2):215–28.

    Article  PubMed  CAS  Google Scholar 

  42. Bala V, Rao S, Li P, Wang S, Prestidge CA. Lipophilic prodrugs of SN38: synthesis and in vitro characterization toward oral chemotherapy. Mol Pharm. 2016;13(1):287–94.

    Article  PubMed  CAS  Google Scholar 

  43. Yu H, Xia D, Zhu Q, Zhu C, Chen D, Gan Y. Supersaturated polymeric micelles for oral cyclosporine A delivery. Eur J Pharm Biopharm. 2013;85(3 Pt B):1325–36.

    Article  PubMed  CAS  Google Scholar 

  44. Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials. 2010;31(25):6597–611.

    Article  PubMed  CAS  Google Scholar 

  45. Thakral NK, Ray AR, Bar-Shalom D, Eriksson AH, Majumdar DK. Soluplus-solubilized citrated camptothecin—a potential drug delivery strategy in colon cancer. AAPS PharmSciTech. 2012;13(1):59–66.

    Article  PubMed  CAS  Google Scholar 

  46. Wen H, Morris KR, Park K. Study on the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystals: partial dissolution pattern change. J Pharm Sci. 2005;94(10):2166–74.

    Article  PubMed  CAS  Google Scholar 

  47. Shi NQ, Lai HW, Zhang Y, Feng B, Xiao X, Zhang HM, et al. On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology. Pharm Dev Technol. 2016:1–14.

  48. Fule R, Amin P. Development and evaluation of lafutidine solid dispersion via hot melt extrusion: investigating drug-polymer miscibility with advanced characterisation. Asian J Pharm Sci. 2014;9(2):92–106.

    Article  Google Scholar 

  49. Kothari K, Ragoonanan V, Suryanarayanan R. The role of drug-polymer hydrogen bonding interactions on the molecular mobility and physical stability of nifedipine solid dispersions. Mol Pharm. 2015;12(1):162–70.

    Article  PubMed  CAS  Google Scholar 

  50. Gupta NK, Dixit VK. Bioavailability enhancement of curcumin by complexation with phosphatidyl choline. J Pharm Sci. 2011;100(5):1987–95.

    Article  PubMed  CAS  Google Scholar 

  51. Small GW, Siddarth P, Li Z, Miller KJ, Ercoli L, Emerson ND, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: a double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266–77.

    Article  PubMed  Google Scholar 

  52. Rainey-Smith SR, Brown BM, Sohrabi HR, Shah T, Goozee KG, Gupta VB, et al. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016;115(12):2106–13.

    Article  PubMed  CAS  Google Scholar 

  53. Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. 2015;29(5):642–51.

    Article  PubMed  CAS  Google Scholar 

  54. Parikh A, Kathawala K, Li J, Chen C, Shan Z, Cao X, Garg S, Zhou XF. Self-nanomicellizing solid dispersion of Edaravone: part II: in-vivo assessment of efficacy against behavior deficits and safety in Alzheimer’s disease model, drug design, development and therapy 2018.

  55. Zeng YQ, Wang YJ, Zhou XF. Effects of (-)epicatechin on the pathology of APP/PS1 transgenic mice. Front Neurol. 2014;5:69.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kakkar V, Singh S, Singla D, Kaur IP. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol Nutr Food Res. 2011;55(3):495–503.

    Article  PubMed  CAS  Google Scholar 

  57. Ghosh SS, He H, Wang J, Gehr TW, Ghosh S. Curcumin-mediated regulation of intestinal barrier function: the mechanism underlying its beneficial effects. Tissue Barriers. 2018;6(1):e1425085.

    Article  PubMed  CAS  Google Scholar 

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The authors would like to acknowledge the financial support from Fujian Kangshimei Co, China, for the present research. Prof. Xin-Fu Zhou is grateful for the NHMRC fellowship. Ankit Parikh is obliged for the University President’s Scholarships from University of South Australia. Also, we thank Lyn Waterhouse from Adelaide Microscopy, The University of Adelaide for the technical support in transmission electron microscopy analysis, Dr. Binoy Sarkar from Centre for Environmental Risk Assessment and Remediation, University of South Australia for X-ray diffraction study, Dr. Nobuyuki Kawashima and Dr. Steve McInnes from Future Industries Institute, University of South Australia, for scanning electron microscopy and differential scanning calorimetry analysis, respectively, H. Md. Morshed Alam (BASF Australia Ltd) for generously providing SOL, and Stephen Philip, a Ph.D. candidate, from School of Pharmacy and Medical Sciences, University of South Australia, for NMR study. The Reid animal house staff members from University of South Australia are acknowledged for generous support in animal work.

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Authors and Affiliations



Sanjay Garg (SG) and Xin-Fu Zhou (XFZ) conceived the project. Ankit Parikh (AP), Krishna Kathawala (KK), Yunmei Song (YS), XFZ, and SG designed the study; AP, KK, and XFZ performed the research; AP, KK, YS, XFZ, and SG analyzed the data; AP, KK, XFZ, and SG wrote the paper.

Corresponding authors

Correspondence to Xin-Fu Zhou or Sanjay Garg.

Ethics declarations

All the animal experiments were approved by local animal ethics committee of the University of South Australia under South Australian Animal Welfare Act 1985 and in accordance with an institutional guideline.

Conflict of interest

Ankit Parikh, Xin-Fu Zhou, and Sanjay Garg are the named inventors of Chinese patent 201610267974.5. Fujian Kangshimei Co, China, owns the intellectual property. There is no other potential conflict of interest relevant to this article.

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Parikh, A., Kathawala, K., Song, Y. et al. Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability. Drug Deliv. and Transl. Res. 8, 1389–1405 (2018).

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