Novel delivery system for natural products: Nano-curcumin formulations

Document Type : Review Article


1 Students Research Committee, Mashhad University of Medical Sciences, Iran

2 Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug.
Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid).
Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially.
Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions.


Main Subjects

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.2007. Bioavailability of curcumin: problems and promises. Mole pharma, 4:807-818
Balogun E, Hoque M, Gong P, Killeen E,Green C, Roberta A, Jawed M.2003. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J, 371:887-895
Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC.2011. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res, 4:1158-1171
Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G. 2010. Efficacy and safety of Meriva(R), a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Alternative medicine review . Altern Med Rev, 15:337-44
Braga ME, Leal PF, Carvalho JE, Meireles MAA.2003. Comparison of yield, composition, and antioxidant activity of turmeric (Curcuma longa L.) extracts obtained using various techniques. J Agric Food Chem, 51:6604-6611
Das RK, Kasoju N, Bora U.2010. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine, 6:153-160
Dubey SK, Sharma AK, Narain U, Misra K, Pati U.2008. Design, synthesis and characterization of some bioactive conjugates of curcumin with glycine, glutamic acid, valine and demethylenated piperic acid and study of their antimicrobial and antiproliferative properties. Eur J Med Chem, 43:1837-46
Esmaili M, Ghaffari SM, Moosavi-Movahedi Z, et al.2011. Beta casein-micelle as a nano vehicle for solubility enhancement of curcumin; food industry application. LWT-food sci tech, 44:2166-2172
Farzadnia M, Ayatollahi H, Hasan-Zade M, Rahimi HR.2013. A Comparative Study of Serum Level of Vascular Cell Adhesion Molecule-1 (sVCAM-1), Intercellular Adhesion Molecule-1(ICAM-1) and High Sensitive C - reactive protein (hs-CRP) in Normal and Pre-eclamptic Pregnancies. Iran J Basic Med Sci, 16:689-93
Gangwar RK, Tomar GB, Dhumale VA, Zinjarde S, Sharma RB, Datar S.2013. Curcumin conjugated silica nanoparticles for improving bioavailability and its anticancer applications. J Agric Food Chem, 61:9632-9637
Ganjali S, Sahebkar A, Mahdipour E, Jamialahmadi K, Torabi S, Akhlaghi S, Ferns G, Parizadeh SM, Ghayour-Mobarhan G .2014. Investigation of the effects of curcumin on serum cytokines in obese individuals: a randomized controlled trial. ScientificWorldJournal, 2014:898361
Gao Y, Li Z, Sun M, Li H, Guo C, Cui J, Li A, Cao F, Xi Y, Lou H, Zhai G..2010. Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer. Drug Dev Ind Pharm, 36:1225-1234.
Garodia P, Ichikawa H, Malani N, Sethi G, Aggarwal BB.2007. From ancient medicine to modern medicine: ayurvedic concepts of health and their role in inflammation and cancer. J Soc Integr Oncol, 5:25-37.
Goel A, Jhurani S, Aggarwal BB.2008. Multi‐targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res, 52:1010-1030.
Hansel W, Aggarwal S, Hammer RP (2009) Curcumin conjugates for treating and preventing cancers. Google Patents
Hatcher H, Planalp R, Cho J, Torti F, Torti S.2008. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci, 65:1631-1652.
He Y, Huang Y, Cheng Y.2010. Structure evolution of curcumin nanoprecipitation from a micromixer. Cryst. Growth Des, 10:1021-1024.
Howles PN.2010. Cholesterol absorption and metabolism. Methods Mol Biol, 602:157-79 .
Hsu C-H, Cheng A-L (2007) Clinical studies with curcumin The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Springer, p 471-480.
Jantarat C.2013. Bioavailability enhancement techniques of herbal medicine: A case example of curcumin. International J Pharmacy and Pharmaceutical Sci, 5:493-500.
Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, Liu S, Dontu G, Wicha MS.2010. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat, 122:777-785.
Kakkar V, Singh S, Singla D, Kaur IP.2011. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol Nutr Food Res, 55:495-503.
Kaminaga Y, Nagatsu A, Akiyama T, Sugimoto N, Yamazaki T, Maitani T, Mizukami H.2003. Production of unnatural glucosides of curcumin with drastically enhanced water solubility by cell suspension cultures of Catharanthus roseus. FEBS Lett, 555:311-316.
Kim DS, Park S-Y, Kim J-Y.2001. Curcuminoids from Curcuma longa L.(Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from βA (1–42) insult. Neurosci Lett, 303:57-61.
Kumar S, Dubey KK, Tripathi S, Fujii M, Misra K Design and synthesis of curcumin-bioconjugates to improve systemic delivery. In: Nucleic acids symposium series, 2000. vol 44. Oxford Univ Press, p 75-76.
Kunnumakkara AB, Anand P, Aggarwal BB.2008. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett, 269:199-225.
Lao CD, Ruffin MT Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE.2006. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med, 6:10.
Li L, Braiteh FS, Kurzrock R.2005. Liposome-encapsulated curcumin. Cancer, 104:1322-1331.
Liu C-H, Chang F-Y.2011. Development and characterization of eucalyptol microemulsions for topic delivery of curcumin. Chem  Pharm Bulletin, (Tokyo), 59:172.
Liu C-H, Chang F-Y, Hung D-K.2011. Terpene microemulsions for transdermal curcumin delivery: effects of terpenes and cosurfactants. Colloids Surf B Biointerfaces, 82:63-70.
Liu J, Chen S, Lv L, Song L, Guo S, Huang S.2013. Recent progress in studying curcumin and its nano-preparations for cancer therapy. Curr Pharm Des, 19:1974-1993.
Maheshwari RK, Singh AK, Gaddipati J, Srimal RC.2006. Multiple biological activities of curcumin: a short review. Life sci, 78:2081-2087.
Manju S, Sreenivasan K.2011. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability. J Colloid Interface Sci, 359:318-325.
Mukerjee A, Vishwanatha JK.2009. Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Res, 29:3867-387.5
Mulik RS, Mönkkönen J, Juvonen RO, Mahadik KR, Paradkar AR.2010. Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis. Int J Pharm, 398:190-203.
Muqbil I, Masood A, Sarkar FH, Mohammad RM, Azmi AS.2011. Progress in nanotechnology based approaches to enhance the potential of chemopreventive agents. Cancers, 3:428-445.
O'Shea RS, Dasarathy S, McCullough AJ.2010. Alcoholic liver disease. Hepatology, 51:307-328.
Oskuee RK, Dehshahri A, Shier WT, Ramezani M.2009. Alkylcarboxylate grafting to polyethylenimine: a simple approach to producing a DNA nanocarrier with low toxicity. J Gene Med, 11:921-32 .
Pandey MK, Kumar S, Thimmulappa RK, Parmar VS, Biswal S, Watterson AC.2011. Design, synthesis and evaluation of novel PEGylated curcumin analogs as potent Nrf2 activators in human bronchial epithelial cells. Eur J Pharm Sci, 43:16-24.
Pathak N, Khandelwal S.2008. Comparative efficacy of piperine, curcumin and picroliv against Cd immunotoxicity in mice. Biometals, 21:649-661.
Rachmawati H, Al Shaal L, Muller RH, Keck CM.2013a. Development of curcumin nanocrystal: physical aspects. J Pharm Sci, 102:204-14 .
Rachmawati H, Shaal LA, Müller RH, Keck CM.2013b. Development of curcumin nanocrystal: physical aspects. J pharm sci, 102:204-214.
Rahimi HR, Oskuee RK.2014. Curcumin From Traditional Iranian Medicine to Molecular Medicine. Razavi Int J Med, 2.
Ravichandran R.2013. Development of an Oral Curcumin Nanocrystal Formulation. J Nanotech Eng Med, 3:041007-041007 .
Ravindran J, Prasad S, Aggarwal BB.2009. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J, 11:495-510.
Roco MC.2003. Nanotechnology: convergence with modern biology and medicine. Curr Opin Biotechnol, 14:337-346
Rushworth SA, Ogborne RM, Charalambos CA, O’Connell MA.2006. Role of protein kinase C δ in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun, 341:1007-1016.
Safavy A, Raisch KP, Mantena S, et al.2007. Design and Development of Water-Soluble Curcumin Conjugates as Potential Anticancer Agents. J Med Chem, 50:6284-6288.
Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanapatapee R.2010. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. Eur J Pharm Biopharm, 76:475-485.
Shaikh J, Ankola D, Beniwal V, Singh D, Kumar MR.2009. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci, 37:223-230.
Shamsara J, Ramezani M, Mohammadpour AH.2009. Curcumin as a novel plaque stabilizing agent in prevention of acute coronary syndrome. Iran J Med Hypotheses Ideas, 3:1-6.
Shishodia S, Sethi G, Aggarwal BB.2005. Curcumin: getting back to the roots. Ann N Y Acad Sci, 1056:206-21.7
Simoni E, Bergamini C, Fato R, et al.2010. Polyamine Conjugation of Curcumin Analogues toward the Discovery of Mitochondria-Directe Neuroprotective Agents. J Med Chem, 53:7264-7268.
Smalley R.2003. Nanotechnology. Chemical & Engineering News, 81:37-42.
Smithson KW, Millar DB, Jacobs LR, Gray GM.1981. Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat? Science, 214:1241-1244.
Soni K, Kuttan R.1992. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol, 36:273-273.
Sou K, Inenaga S, Takeoka S, Tsuchida E.2008. Loading of curcumin into macrophages using lipid-based nanoparticles. Int J Pharm, 352:287-293.
Takahashi M, Uechi S, Takara K, Asikin Y, Wada K.2009. Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. J Agric Food Chem, 57:9141-9146.
Tang H, Murphy CJ, Zhang B, et al.2010. Curcumin polymers as anticancer conjugates. Biomaterials, 31:7139-7149.
Thamake S, Raut S, 2, Ranjan A, Gryczynski Z, Vishwanatha J.2011. Surface functionalization of PLGA nanoparticles by non-covalent insertion of a homo-bifunctional spacer for active targeting in cancer therapy. Nanotechnology, 22:035101.
Tiyaboonchai W, Tungpradit W, Plianbangchang P.2007. Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. Int J Pharm, 337:299-306.
Tønnesen HH, Másson M, Loftsson T.2002. Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int J Pharm, 244:127-135.
Tsai Y-M, Chien C-F, Lin L-C, Tsai T-H.2011. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood–brain barrier penetration. Int J Pharm, 416:331-338.
Usta M, Wortelboer HM, Vervoort J, et al.2007. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells. Chem Res Toxicol, 20:1895-1902.
Vareed SK, Kakarala M, Ruffin MT, et al.2008. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev, 17:1411-1417.
Venkatesha SH, Berman BM, Moudgil KD.2011. Herbal medicinal products target defined biochemical and molecular mediators of inflammatory autoimmune arthritis. Bioorg Med Chem, 19:21-29.
Wang R, Xu Y, Wu H-L, et al.2008. The antidepressant effects of curcumin in the forced swimming test involve 5-HT 1 and 5-HT 2 receptors. Eur J Pharmacol, 578:43-50.
Yallapu MM, Jaggi M, Chauhan SC.2012. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today, 17:71-80.
Yang K-Y, Lin L-C, Tseng T-Y, Wang S-C, Tsai T-H.2007. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC–MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci, 853:183-189.
Yih TC, Wei C.2005. Nanomedicine in cancer treatment. Nanomedicine: Nanotechnology, Biology and Medicine, 1:191-192.