Nanocurcumin: A Promising Candidate for Therapeutic Applications

Curcuma longa is an important medicinal plant and a spice in Asia. Curcumin (diferuloylmethane) is a hydrophobic bioactive ingredient found in a rhizome of the C. longa. It has drawn immense attention in recent years for its variety of biological and pharmacological action. However, its low water solubility, poor bioavailability, and rapid metabolism represent major drawbacks for its successful therapeutic applications. Hence, researchers have attempted to enhance the biological and pharmacological activity of curcumin and overcome its drawbacks by efficient delivery systems, particularly nanoencapsulation. Research efforts so far and data from the available literature have shown a satisfactory potential of nanorange formulations of curcumin (Nanocurcumin), it increases all the biological and pharmacological benefits of curcumin, which was not significantly possible earlier. For the synthesis of nanocurcumin, an array of techniques has been developed and each technique has its own advantages and individual characteristics. The two most popular and effective techniques are ionic gelation and antisolvent precipitation. So far, many curcumin nanoformulations have been developed to enhance curcumin delivery, thereby overcoming the low therapeutic effects. However, most of the nanoformulation of curcumin remained at the concept level evidence, thus, several questions and challenges still exist to recommend the nanocurcumin as a promising candidate for therapeutic applications. In this review, we discuss the different curcumin nanoformulation and nanocurcumin implications for different therapeutic applications as well as the status of ongoing clinical trials and patents. We also discuss the research gap and future research directions needed to propose curcumin as a promising therapeutic candidate.

[1]  Yang Li,et al.  Construction of Multilevel Structure for Avian Influenza Virus System Based on Granular Computing , 2017, BioMed research international.

[2]  S. G. Hosseini,et al.  A Review on the Preparation Methods of Superfine Ammonium Perchlorate , 2019 .

[3]  Rupesh Kumar Basniwal,et al.  Improving the Anticancer Activity of Curcumin Using Nanocurcumin Dispersion in Water , 2014, Nutrition and cancer.

[4]  U. Bandyopadhyay,et al.  Turmeric and curcumin: Biological actions and medicinal applications , 2004 .

[5]  Aamir Ahmad,et al.  Inclusion Complex of Novel Curcumin Analogue CDF and β-Cyclodextrin (1:2) and Its Enhanced In Vivo Anticancer Activity Against Pancreatic Cancer , 2012, Pharmaceutical Research.

[6]  M. Najafi,et al.  Curcumin as an anti‐inflammatory agent: Implications to radiotherapy and chemotherapy , 2018, Journal of cellular physiology.

[7]  M. K. Swamy,et al.  Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes , 2016, Molecules.

[8]  J. Friedman,et al.  Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[9]  A. Ingle,et al.  Curcumin and curcumin-loaded nanoparticles: antipathogenic and antiparasitic activities , 2020, Expert review of anti-infective therapy.

[10]  L. Gordon,et al.  Curcumin nanodisk-induced apoptosis in mantle cell lymphoma , 2011, Leukemia & lymphoma.

[11]  K. Chennazhi,et al.  In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  J. Andersen,et al.  Mitochondrial complex I inhibition in Parkinson's disease: how can curcumin protect mitochondria? , 2006, Antioxidants & redox signaling.

[13]  B. Singh,et al.  Synthesis of Alginate-Curcumin Nanocomposite and Its Protective Role in Transgenic Drosophila Model of Parkinson's Disease , 2013, ISRN pharmacology.

[14]  B. Aggarwal,et al.  Curcumin as "Curecumin": from kitchen to clinic. , 2008, Biochemical pharmacology.

[15]  Tzong-Ming Shieh,et al.  Curcumin-loaded nanoparticles induce apoptotic cell death through regulation of the function of MDR1 and reactive oxygen species in cisplatin-resistant CAR human oral cancer cells. , 2013, International journal of oncology.

[16]  B. Aggarwal,et al.  Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. , 2009, Trends in pharmacological sciences.

[17]  S. Jafari,et al.  Application of different nanocarriers for encapsulation of curcumin , 2018, Critical reviews in food science and nutrition.

[18]  P. I. Costa,et al.  Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin‐diabetic rats , 2019, Phytotherapy research : PTR.

[19]  M. Morbidelli,et al.  Polymer nanoparticles for the intravenous delivery of anticancer drugs: the checkpoints on the road from the synthesis to clinical translation. , 2018, Nanoscale.

[20]  G. Sethi,et al.  Curcumin Delivery Mediated by Bio-Based Nanoparticles: A Review , 2020, Molecules.

[21]  M. Harirchian,et al.  Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial , 2018, Neurotherapeutics.

[22]  Wael K Al-Delaimy,et al.  Curcumin Content of Turmeric and Curry Powders , 2006, Nutrition and cancer.

[23]  Cornelia M Keck,et al.  Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles. , 2004, Journal of biotechnology.

[24]  Wim E Hennink,et al.  Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. , 2014, Biomaterials.

[25]  Y. Panahi,et al.  Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial , 2016, Journal of dietary supplements.

[26]  V. Karathanos,et al.  Stability and release properties of curcumin encapsulated in Saccharomyces cerevisiae, β-cyclodextrin and modified starch , 2011 .

[27]  Aniket Gade,et al.  Potential applications of curcumin and curcumin nanoparticles: from traditional therapeutics to modern nanomedicine , 2015 .

[28]  K. Rostamizadeh,et al.  Enhanced cytotoxic activity of curcumin on cancer cell lines by incorporating into gold/chitosan nanogels , 2019, Materials Chemistry and Physics.

[29]  Aamir Ahmad,et al.  Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway , 2020, International journal of molecular sciences.

[30]  M. Gremião,et al.  Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery , 2016, International journal of nanomedicine.

[31]  Abhishek Sahu,et al.  Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells. , 2008, Biomacromolecules.

[32]  G. Padmanaban,et al.  Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria , 2017, Scientific Reports.

[33]  K. Chennazhi,et al.  Anti-cancer, pharmacokinetics and tumor localization studies of pH-, RF- and thermo-responsive nanoparticles. , 2015, International journal of biological macromolecules.

[34]  N. Rogers,et al.  Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen‐presenting cells , 2012, British journal of pharmacology.

[35]  C. Mohanty,et al.  Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model. , 2012, Molecular pharmaceutics.

[36]  F. Gramatica,et al.  Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells. , 2014, Molecular pharmaceutics.

[37]  Tarun K. Maji,et al.  Controlled release of curcumin from thiolated starch-coated iron oxide magnetic nanoparticles: An in vitro evaluation , 2017 .

[38]  Youn-Chul Kim,et al.  Dimethoxycurcumin, a Synthetic Curcumin Analogue, Induces Heme Oxygenase-1 Expression through Nrf2 Activation in RAW264.7 Macrophages , 2008, Journal of clinical biochemistry and nutrition.

[39]  B. Topçu,et al.  The effects of topical treatment with curcumin on burn wound healing in rats , 2012, Journal of Molecular Histology.

[40]  Shadi F Othman,et al.  Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications , 2012, International journal of nanomedicine.

[41]  B. Aggarwal,et al.  Role of nuclear factor-κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents , 2011, Experimental biology and medicine.

[42]  L. Gholami,et al.  EEffects of nano-curcumin and curcumin on the oxidant and antioxidant system of the liver mitochondria in aluminum phosphide-induced experimental toxicity , 2020 .

[43]  Ling Li,et al.  Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis. , 2013, International journal of pharmaceutics.

[44]  R. Pochampally,et al.  Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[45]  T. Giri Alginate Containing Nanoarchitectonics for Improved Cancer Therapy , 2016 .

[46]  Durg Vijay Singh,et al.  Curcumin conjugates induce apoptosis via a mitochondrion dependent pathway in MCF-7 and MDA-MB-231 cell lines. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[47]  J. Vishwanatha,et al.  Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. , 2009, Anticancer research.

[48]  M. R. Kumar,et al.  Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[49]  R. Srimal,et al.  Pharmacology of diferuloyl methane (curcumin), a non‐steroidal anti‐inflammatory agent * , 1973, The Journal of pharmacy and pharmacology.

[50]  B. Rolando,et al.  Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells , 2020, Pharmaceutics.

[51]  H. Uno,et al.  On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activity. , 2000, Organic letters.

[52]  Ling Li,et al.  Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. , 2013, Biomaterials.

[53]  Robert O Ryan,et al.  ApoE enhances nanodisk-mediated curcumin delivery to glioblastoma multiforme cells. , 2014, Nanomedicine.

[54]  G. Rimbach,et al.  Curcumin--from molecule to biological function. , 2012, Angewandte Chemie.

[55]  B. Aggarwal,et al.  Curcumin: Getting Back to the Roots , 2005, Annals of the New York Academy of Sciences.

[56]  Chun-ching Lin,et al.  Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. , 2010, Journal of agricultural and food chemistry.

[57]  M. Srinivasan,et al.  Hypocholesteremic effect of curcumin in induced hypercholesteremic rats. , 1971, Indian journal of experimental biology.

[58]  M. Chikindas,et al.  Antimicrobial efficacy of curcumin nanoparticles against Listeria monocytogenes is mediated by surface charge , 2017 .

[59]  C. Mohanty,et al.  The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. , 2010, Biomaterials.

[60]  A. Maitra,et al.  A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors , 2011, Cancer biology & therapy.

[61]  P. Mediratta,et al.  Modulation of pentylenetetrazole-induced kindling and oxidative stress by curcumin in mice. , 2011, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[62]  Siqi Guo Encapsulation of curcumin into β-cyclodextrins inclusion: A review , 2019, E3S Web of Conferences.

[63]  Tak W. Kee,et al.  Excited-state intramolecular hydrogen atom transfer of curcumin in surfactant micelles. , 2010, The journal of physical chemistry. B.

[64]  N. N. Pathak,et al.  Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. , 2014, International immunopharmacology.

[65]  Wenyuan Gao,et al.  Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin. , 2016, Environmental toxicology and pharmacology.

[66]  W. Chng,et al.  Curcumin Sensitizes Acute Promyelocytic Leukemia Cells to Unfolded Protein Response–Induced Apoptosis by Blocking the Loss of Misfolded N-CoR Protein , 2011, Molecular Cancer Research.

[67]  F. Abas,et al.  Molecular Pathways Modulated by Curcumin Analogue, Diarylpentanoids in Cancer , 2019, Biomolecules.

[68]  Shaodong Guo,et al.  Nano‐curcumin safely prevents streptozotocin‐induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus , 2017, British journal of pharmacology.

[69]  S. Flora,et al.  Curcumin encapsulated in chitosan nanoparticles: a novel strategy for the treatment of arsenic toxicity. , 2012, Chemico-biological interactions.

[70]  E. Tsiani,et al.  Antidiabetic Properties of Curcumin I: Evidence from In Vitro Studies , 2020, Nutrients.

[71]  N. Canilho,et al.  Core-shell microcapsules of solid lipid nanoparticles and mesoporous silica for enhanced oral delivery of curcumin. , 2016, Colloids and surfaces. B, Biointerfaces.

[72]  P. Zou,et al.  ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer , 2015, Oncotarget.

[73]  H. Suleria,et al.  Cucurmin, anticancer, & antitumor perspectives: A comprehensive review , 2018, Critical reviews in food science and nutrition.

[74]  K. Gupta,et al.  Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway. , 2014, ACS nano.

[75]  P. Groundwater,et al.  A Carbocyclic Curcumin Inhibits Proliferation of Gram-Positive Bacteria by Targeting FtsZ. , 2017, Biochemistry.

[76]  M. Lord,et al.  Curcumin-Loading-Dependent Stability of PEGMEMA-Based Micelles Affects Endocytosis and Exocytosis in Colon Carcinoma Cells. , 2016, Molecular pharmaceutics.

[77]  P. Subramani,et al.  Curcumin Nanotechnologies and Its Anticancer Activity , 2017, Nutrition and cancer.

[78]  Yifan Zhang,et al.  Liposome co-encapsulation as a strategy for the delivery of curcumin and resveratrol. , 2019, Food & function.

[79]  B. Aggarwal,et al.  Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials , 2012, The AAPS Journal.

[80]  K. S. Kumar,et al.  Turmeric: a herbal and traditional medicine. , 2009 .

[81]  Liqun Yang,et al.  Long-circulating zein-polysulfobetaine conjugate-based nanocarriers for enhancing the stability and pharmacokinetics of curcumin. , 2020, Materials science & engineering. C, Materials for biological applications.

[82]  J. Yakhmi,et al.  Interfacial engineering of nanoparticles for cancer therapeutics , 2017 .

[83]  Á. Alonso-Moraga,et al.  In vivo and in vitro evaluation for nutraceutical purposes of capsaicin, capsanthin, lutein and four pepper varieties. , 2016, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[84]  S. Suresh,et al.  Nanocurcumin ameliorates Staphylococcus aureus‐induced mastitis in mouse by suppressing NF‐&kgr;B signaling and inflammation , 2018, International immunopharmacology.

[85]  A. Boddy,et al.  Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions , 2017, Expert opinion on drug metabolism & toxicology.

[86]  O. P. Sharma Antioxidant activity of curcumin and related compounds. , 1976, Biochemical pharmacology.

[87]  Jixiang Zhu,et al.  Supercritical carbon dioxide-developed silk fibroin nanoplatform for smart colon cancer therapy , 2017, International journal of nanomedicine.

[88]  R. Das,et al.  Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[89]  O. Werz,et al.  Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1 , 2009, Molecular Cancer Therapeutics.

[90]  Shile Huang,et al.  Pharmacological and clinical properties of curcumin , 2011 .

[91]  D. Panda,et al.  Probing the binding site of curcumin in Escherichia coli and Bacillus subtilis FtsZ--a structural insight to unveil antibacterial activity of curcumin. , 2010, European journal of medicinal chemistry.

[92]  C. A. Damalas,et al.  Potential Uses of Turmeric ('Curcuma longa') Products as Alternative Means of Pest Management in Crop Production , 2011 .

[93]  K. Lee,et al.  Recent advances in the investigation of curcuminoids , 2008, Chinese medicine.

[94]  B. Liagre,et al.  Development of curcumin-cyclodextrin/cellulose nanocrystals complexes: New anticancer drug delivery systems. , 2016, Bioorganic & medicinal chemistry letters.

[95]  M. Broekgaarden,et al.  The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer , 2014, Pharmacological Reviews.

[96]  D. Mcclements,et al.  Core-shell biopolymer nanoparticle delivery systems: synthesis and characterization of curcumin fortified zein-pectin nanoparticles. , 2015, Food chemistry.

[97]  M. Bhattacharya,et al.  Curcumin as potential therapeutic natural product: a nanobiotechnological perspective , 2016, The Journal of pharmacy and pharmacology.

[98]  J. Miłobȩdzka,et al.  Zur Kenntnis des Curcumins , 1897 .

[99]  M. E. Norhaizan,et al.  Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer , 2019, Molecules.

[100]  K. Mahadik,et al.  Development of curcuminoids loaded poly(butyl) cyanoacrylate nanoparticles: Physicochemical characterization and stability study. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[101]  Xiang-chun Shen,et al.  A W/O emulsion mediated film dispersion method for curcumin encapsulated pH-sensitive liposomes in the colon tumor treatment , 2018, Drug development and industrial pharmacy.

[102]  G. Jagetia,et al.  Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation , 2015, Antioxidants.

[103]  B. Aggarwal,et al.  Curcumin and cancer: an "old-age" disease with an "age-old" solution. , 2008, Cancer letters.

[104]  C. Ha,et al.  Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti cancer drug delivery. , 2015, International journal of pharmaceutics.

[105]  J. Aukunuru,et al.  Preparation and Characterization of PEG-albumin-curcumin Nanoparticles Intended to Treat Breast Cancer , 2016, Indian journal of pharmaceutical sciences.

[106]  A. Shimatsu,et al.  Clinical Application of “Curcumin”, a Multi-Functional Substance , 2012 .

[107]  D. Brocks,et al.  High-performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin. , 2007, Biomedical chromatography : BMC.

[108]  Lu Tie,et al.  Curcumin‐loaded poly(ε‐caprolactone) nanofibres: Diabetic wound dressing with anti‐oxidant and anti‐inflammatory properties , 2009, Clinical and experimental pharmacology & physiology.

[109]  Soodabeh Davaran,et al.  Liposome: classification, preparation, and applications , 2013, Nanoscale Research Letters.

[110]  M. Kaliňák,et al.  Antioxidant properties of curcuminoids isolated from Curcuma longa L. , 2016 .

[111]  Dongwei Zhang,et al.  Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis , 2017, BioMed research international.

[112]  L. Gordon,et al.  Curcumin nanodisks: formulation and characterization. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[113]  M. Tambuwala,et al.  Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression of HIF-1α and Nuclear p65 (Rel A). , 2017, Current drug delivery.

[114]  E. Srivatsan,et al.  Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma , 2011, Molecular Cancer.

[115]  Jen-kun Lin Molecular targets of curcumin. , 2007, Advances in experimental medicine and biology.

[116]  A. Conney,et al.  Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. , 1991, Cancer research.

[117]  T. Dziubla,et al.  Single step synthesis, characterization and applications of curcumin functionalized iron oxide magnetic nanoparticles. , 2016, Materials science & engineering. C, Materials for biological applications.

[118]  R. Zhang,et al.  Fabrication of Stable and Self-Assembling Rapeseed Protein Nanogel for Hydrophobic Curcumin Delivery. , 2019, Journal of agricultural and food chemistry.

[119]  Zhaoxin Lu,et al.  Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens. , 2009, International journal of food microbiology.

[120]  L. Freitas,et al.  Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity , 2015, AAPS PharmSciTech.

[121]  Jinchao Zhang,et al.  Synthesis, characterization and ROS-mediated antitumor effects of palladium(II) complexes of curcuminoids. , 2018, European journal of medicinal chemistry.

[122]  A. Ranjbar,et al.  Evaluation of the protective effects of curcumin and nanocurcumin against lung injury induced by sub-acute exposure to paraquat in rats , 2019, Toxin Reviews.

[123]  Mohammed S. Alqahtani,et al.  Synthesis of novel biodegradable methoxy poly(ethylene glycol)-zein micelles for effective delivery of curcumin. , 2012, Molecular pharmaceutics.

[124]  Ajazuddin,et al.  Biodegradable IPN hydrogel beads of pectin and grafted alginate for controlled delivery of diclofenac sodium , 2013, Journal of Materials Science: Materials in Medicine.

[125]  T. Mohamed,et al.  Curcumin Binding to Beta Amyloid: A Computational Study , 2015, Chemical biology & drug design.

[126]  E. Licărete,et al.  Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells , 2018, Pharmacological reports : PR.

[127]  Xiaoyuan Chen,et al.  Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. , 2011, International journal of pharmaceutics.

[128]  M. Srinivasan Effect of curcumin on blood sugar as seen in a diabetic subject. , 1972, Indian journal of medical sciences.

[129]  Yueyue Wang,et al.  Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in Breast Cancer , 2018, Molecules.

[130]  W. Chrzanowski,et al.  Curcumin as a wound healing agent. , 2014, Life sciences.

[131]  Ji-Yun Kim,et al.  Nanosphere Loaded With Curcumin Inhibits the Gastrointestinal Cell Death Signaling Pathway Induced by the Foodborne Pathogen Vibrio vulnificus , 2020, Cells.

[132]  H. Atreya,et al.  Curcumin nanoconjugate inhibits aggregation of N-terminal region (Aβ-16) of an amyloid beta peptide , 2018 .

[133]  N. Seeram,et al.  Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations. , 2014, Journal of medicinal food.

[134]  Rupesh Kumar Basniwal,et al.  Curcumin nanoparticles: preparation, characterization, and antimicrobial study. , 2011, Journal of agricultural and food chemistry.

[135]  Eun-Mi Kim,et al.  Curcumin Encapsulated Micellar Nanoplatform for Blue Light Emitting Diode Induced Apoptosis as a New Class of Cancer Therapy , 2019, Macromolecular Research.

[136]  Gowthamarajan Kuppusamy,et al.  Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. , 2016, International journal of biological macromolecules.

[137]  D. Kalman,et al.  Curcumin: A Review of Its’ Effects on Human Health , 2017, Foods.

[138]  K. Rostamizadeh,et al.  Curcumin mediated down‐regulation of αVβ3 integrin and up‐regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells , 2018, Phytotherapy research : PTR.

[139]  S. Nair,et al.  Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route. , 2012, Nanoscale.

[140]  D. Selkoe Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[141]  S. Jovanovic,et al.  H-Atom Transfer Is A Preferred Antioxidant Mechanism of Curcumin , 1999 .

[142]  J. Pizzicannella,et al.  Curcumin/Liposome Nanotechnology as Delivery Platform for Anti-inflammatory Activities via NFkB/ERK/pERK Pathway in Human Dental Pulp Treated With 2-HydroxyEthyl MethAcrylate (HEMA) , 2019, Front. Physiol..

[143]  D. Cui,et al.  Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles , 2012, International journal of nanomedicine.

[144]  Aliakbar Alizadeh,et al.  Effect of 6 Weeks of High Intensity Interval Training with Nano curcumin Supplement on Antioxidant Defense and Lipid Peroxidation in Overweight Girls- Clinical Trial , 2020 .

[145]  P. M. Abraham,et al.  In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation. , 2013, Nanoscale.

[146]  Shobhona Sharma,et al.  Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and toxicological evaluation. , 2010, Journal of pharmaceutical sciences.

[147]  Neeraj Kumar,et al.  Nanonization of curcumin by antisolvent precipitation: process development, characterization, freeze drying and stability performance. , 2014, International journal of pharmaceutics.

[148]  S. Rajasekaran Therapeutic potential of curcumin in gastrointestinal diseases. , 2011, World journal of gastrointestinal pathophysiology.

[149]  R. Jayakumar,et al.  Synthesis, characterization and biological activities of curcumin nanospheres. , 2014, Journal of biomedical nanotechnology.

[150]  I. Kaur,et al.  Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. , 2011, Molecular nutrition & food research.

[151]  N. Yaegashi,et al.  Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells , 2013, International Journal of Gynecologic Cancer.

[152]  A. Tiwari,et al.  Nanocurcumin: a promising therapeutic advancement over native curcumin. , 2013, Critical reviews in therapeutic drug carrier systems.

[153]  A. Prokop,et al.  Nanovehicular intracellular delivery systems. , 2008, Journal of pharmaceutical sciences.

[154]  M. Darroudi,et al.  Synthesis of nano curcumin using black pepper oil by O/W Nanoemulsion Technique and investigation of their biological activities , 2018, LWT.

[155]  Rongjun Chen,et al.  A New Strategy for Intestinal Drug Delivery via pH-Responsive and Membrane-Active Nanogels. , 2018, ACS applied materials & interfaces.

[156]  Xiang-xiang Shi,et al.  Curcumin attenuates endothelial cell fibrosis through inhibiting endothelial–interstitial transformation , 2020, Clinical and experimental pharmacology & physiology.

[157]  Y. Kwon Curcumin as a cancer chemotherapy sensitizing agent , 2014, Journal of the Korean Society for Applied Biological Chemistry.

[158]  P. García-Casillas,et al.  Magnetite Nanoparticles Coated with PEG 3350-Tween 80: In Vitro Characterization Using Primary Cell Cultures , 2020, Polymers.

[159]  J. Safari,et al.  Base-free green synthesis of copper(II) oxide nanoparticles using highly cross-linked poly(curcumin) nanospheres: synergistically improved antimicrobial activity , 2019, Research on Chemical Intermediates.

[160]  S. Punitha,et al.  Solid Dispersions: A Review , 2011 .

[161]  N. Škalko-Basnet,et al.  Liposomal delivery system enhances anti-inflammatory properties of curcumin. , 2012, Journal of pharmaceutical sciences.

[162]  Toby C. Cornish,et al.  A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation , 2011, Laboratory Investigation.

[163]  S. Nakornchai,et al.  Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. , 2007, Biological & pharmaceutical bulletin.

[164]  Ravi R. Patel,et al.  Curcumin-polymeric nanoparticles against colon-26 tumor-bearing mice: cytotoxicity, pharmacokinetic and anticancer efficacy studies , 2016, Drug development and industrial pharmacy.

[165]  C. Sharma,et al.  In vitro cytotoxicity and cellular uptake of curcumin-loaded Pluronic/Polycaprolactone micelles in colorectal adenocarcinoma cells , 2013, Journal of biomaterials applications.

[166]  W. Khalil,et al.  Antitumor Activity of Curcumin-Green Synthesized Gold Nanoparticles: In Vitro Study , 2019, BioNanoScience.

[167]  M. Ohno,et al.  BACE1 Deficiency Rescues Memory Deficits and Cholinergic Dysfunction in a Mouse Model of Alzheimer's Disease , 2004, Neuron.

[168]  P. Rojsitthisak,et al.  Curcumin diethyl disuccinate encapsulated in chitosan/alginate nanoparticles for improvement of its in vitro cytotoxicity against MDA-MB-231 human breast cancer cells. , 2016, Die Pharmazie.

[169]  Jin Yuan,et al.  Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-κB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice , 2018, Inflammation.

[170]  J. Darko,et al.  Synthesis of curcumin-functionalized gold nanoparticles and cytotoxicity studies in human prostate cancer cell line , 2018, Applied Nanoscience.

[171]  V. Menon,et al.  Antioxidant and anti-inflammatory properties of curcumin. , 2007, Advances in experimental medicine and biology.

[172]  N. Trang,et al.  EFFECT OF NANOCURCUMIN PARTICLES PREPARED BY TOP-DOWN METHOD ON CCl4- INDUCED HEPATIC FIBROSIS MICE , 2013 .

[173]  Raju C Reddy,et al.  Curcumin-Loaded Apotransferrin Nanoparticles Provide Efficient Cellular Uptake and Effectively Inhibit HIV-1 Replication In Vitro , 2011, PloS one.

[174]  K. Chopra,et al.  Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[175]  J. Friedman,et al.  Fabrication of biodegradable PEG–PLA nanospheres for solubility, stabilization, and delivery of curcumin , 2017, Artificial Cells Nanomedicine and Biotechnology.

[176]  Jinhong Hu,et al.  Curcumin Inhibits Imiquimod-Induced Psoriasis-Like Inflammation by Inhibiting IL-1beta and IL-6 Production in Mice , 2013, PloS one.

[177]  C. Huang,et al.  Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. , 2016, Nanoscale.

[178]  S. Nabavi,et al.  Curcumin and Liver Disease: from Chemistry to Medicine. , 2014, Comprehensive reviews in food science and food safety.

[179]  A. Kumari,et al.  Intranasal curcumin protects against LPS-induced airway remodeling by modulating toll-like receptor-4 (TLR-4) and matrixmetalloproteinase-9 (MMP-9) expression via affecting MAP kinases in mouse model , 2018, Inflammopharmacology.

[180]  N. Kiaie,et al.  Anti-fibrotic effects of curcumin and some of its analogues in the heart , 2019, Heart Failure Reviews.

[181]  K. Grasing,et al.  GRK5 Deficiency Accelerates β-Amyloid Accumulation in Tg2576 Mice via Impaired Cholinergic Activity* , 2010, The Journal of Biological Chemistry.

[182]  Wenjing Zhang,et al.  Apoptotic effect of green synthesized gold nanoparticles from Curcuma wenyujin extract against human renal cell carcinoma A498 cells , 2019, International journal of nanomedicine.

[183]  S. Vinogradov,et al.  Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for the targeting of CD44-positive and drug-resistant tumors. , 2013, Bioconjugate chemistry.

[184]  Ling Li,et al.  Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo , 2015, Scientific Reports.

[185]  H. Park,et al.  Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[186]  J. Pedraza-Chaverri,et al.  Renoprotective effect of the antioxidant curcumin: Recent findings , 2013, Redox biology.

[187]  Murali M. Yallapu,et al.  Curcumin nanoformulations: a future nanomedicine for cancer. , 2012, Drug discovery today.

[188]  K. Makabe,et al.  Design, synthesis, and evaluation of a water soluble C5-monoketone type curcumin analogue as a potent amyloid β aggregation inhibitor. , 2019, Bioorganic & medicinal chemistry letters.

[189]  M. Sadeghizadeh,et al.  Dendrosomal nanocurcumin and exogenous p53 can act synergistically to elicit anticancer effects on breast cancer cells. , 2018, Gene.

[190]  O. Soliman,et al.  Water-soluble Complex of Curcumin with Cyclodextrins: Enhanced Physical Properties For Ocular Drug Delivery. , 2017, Current drug delivery.

[191]  N. Schizas,et al.  Potential anticancer properties and mechanisms of action of curcumin. , 2015, Anticancer research.

[192]  Yongqiang Zhang,et al.  A novel synthesis of selenium nanoparticles encapsulated PLGA nanospheres with curcumin molecules for the inhibition of amyloid β aggregation in Alzheimer's disease. , 2019, Journal of photochemistry and photobiology. B, Biology.

[193]  I. Tomuță,et al.  Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach , 2017, Drug design, development and therapy.

[194]  Ling Yuan,et al.  Preparation of Curcumin-Loaded Liposomes and Evaluation of Their Skin Permeation and Pharmacodynamics , 2012, Molecules.

[195]  Hongyu Zhou,et al.  The targets of curcumin. , 2011, Current drug targets.

[196]  Xia Zhao,et al.  Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. , 2011, Nanoscale.

[197]  Lin Li,et al.  Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods , 2012, Journal of Nanoparticle Research.

[198]  Hanmin Li,et al.  Antitumor activities of novel glycyrrhetinic acid-modified curcumin-loaded cationic liposomes in vitro and in H22 tumor-bearing mice , 2018, Drug delivery.

[199]  A. Alizadeh,et al.  Nanotechnology-Applied Curcumin for Different Diseases Therapy , 2014, BioMed research international.

[200]  H. Rupasinghe,et al.  Curcumin and Its Carbocyclic Analogs: Structure-Activity in Relation to Antioxidant and Selected Biological Properties , 2013, Molecules.

[201]  Vincent M Rotello,et al.  The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles. , 2010, Small.

[202]  E. Yıldız,et al.  Synthesis of curcumin complexes with iron(III) and manganese(II), and effects of curcumin–iron(III) on Alzheimer's disease , 2018 .

[203]  Sanghyo Kim,et al.  Synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery, and theranostic applications. , 2019, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[204]  G. Balogh,et al.  Solubility, Delivery and ADME Problems of Drugs and Drug-Candidates , 2018 .

[205]  Rajalakshmi.,et al.  A Review on the preparation methods of Curcumin Nanoparticles , 2018 .

[206]  K. Rostamizadeh,et al.  Magnetic nanoparticles decorated with PEGylated curcumin as dual targeted drug delivery: Synthesis, toxicity and biocompatibility study. , 2019, Materials science & engineering. C, Materials for biological applications.

[207]  K. Shahanipour,et al.  Curcumin as an Environmental Potent Antioxidant Decreases Risk of Arthrosclerosis , 2017 .

[208]  Yiguang Jin,et al.  Curcumin solid dispersion‐loaded in situ hydrogels for local treatment of injured vaginal bacterial infection and improvement of vaginal wound healing , 2019, The Journal of pharmacy and pharmacology.

[209]  B. Forbes,et al.  Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[210]  I. Haworth,et al.  A curcumin-diglutaric acid conjugated prodrug with improved water solubility and antinociceptive properties compared to curcumin , 2018, Bioscience, biotechnology, and biochemistry.

[211]  J. Szejtli Introduction and General Overview of Cyclodextrin Chemistry. , 1998, Chemical reviews.

[212]  G. Mahady,et al.  Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. , 2002, Anticancer research.

[213]  P. Rojsitthisak,et al.  Effects of preparation parameters on the characteristics of chitosan–alginate nanoparticles containing curcumin diethyl disuccinate , 2015 .

[214]  V. Karathanos,et al.  Microencapsulation of curcumin in cells of Saccharomyces cerevisiae , 2011 .

[215]  J. Vadgama,et al.  A novel curcumin analog inhibits canonical and non-canonical functions of telomerase through STAT3 and NF-κB inactivation in colorectal cancer cells , 2019, Oncotarget.

[216]  M. Ganjali,et al.  Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery , 2018, Journal of biomaterials science. Polymer edition.

[217]  Md. Reazul Islam,et al.  Nanotechnology based approaches in cancer therapeutics , 2014 .

[218]  Wendy van de Luijtgaarden,et al.  Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response , 2013, Front. Oncol..

[219]  P. Maiti,et al.  Solid lipid curcumin particles provide greater anti-amyloid, anti-inflammatory and neuroprotective effects than curcumin in the 5xFAD mouse model of Alzheimer’s disease , 2018, BMC Neuroscience.

[220]  Jayme L. Dahlin,et al.  The Essential Medicinal Chemistry of Curcumin , 2017, Journal of medicinal chemistry.

[221]  Steven P. Cohen,et al.  Transforaminal Epidural Steroid Injections for Treating Lumbosacral Radicular Pain from Herniated Intervertebral Discs: A Systematic Review and Meta-Analysis , 2016, Anesthesia and analgesia.

[222]  D. Wolf,et al.  Curcumin: New Insights into an Ancient Ingredient against Cancer , 2019, International journal of molecular sciences.

[223]  N. Altorki,et al.  Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. , 1999, Carcinogenesis.

[224]  Bhaskaran Sasikumar,et al.  Genetic resources of Curcuma: diversity, characterization and utilization , 2005, Plant Genetic Resources.

[225]  P. Morrissey,et al.  Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake. , 2015, Molecular and cellular pharmacology.

[226]  C. Rao Regulation of COX and LOX by curcumin. , 2007, Advances in experimental medicine and biology.

[227]  S. Manju,et al.  Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability. , 2011, Journal of colloid and interface science.

[228]  Peter Wipf,et al.  Nanoparticles in cellular drug delivery. , 2009, Bioorganic & medicinal chemistry.

[229]  K. Yoncheva,et al.  Micellar curcumin improves the antibacterial activity of the alkylphosphocholines erufosine and miltefosine against pathogenic Staphyloccocus aureus strains , 2019, Biotechnology & Biotechnological Equipment.

[230]  A. Vaughan,et al.  Preparation of nanoparticles , 2016 .

[231]  N. Chand,et al.  Nano cellulose dispersed chitosan film with Ag NPs/Curcumin: An in vivo study on Albino Rats for wound dressing. , 2017, International journal of biological macromolecules.

[232]  Seung Eun Lee,et al.  Curcumin Attenuates Acrolein-induced COX-2 Expression and Prostaglandin Production in Human Umbilical Vein Endothelial Cells , 2020, Journal of lipid and atherosclerosis.

[233]  M. Shakibaei,et al.  Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin) , 2019, Nutrients.

[234]  S. Suresh,et al.  Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease. , 2009, The Journal of pharmacy and pharmacology.

[235]  F. Belluti,et al.  Chitosan nanoparticles for lipophilic anticancer drug delivery: Development, characterization and in vitro studies on HT29 cancer cells. , 2016, Colloids and surfaces. B, Biointerfaces.

[236]  S. Bardien,et al.  Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review , 2019, Neuroscience.

[237]  R. Mohan Raj,et al.  Curcumin-loaded layer-by-layer folic acid and casein coated carboxymethyl cellulose/casein nanogels for treatment of skin cancer , 2017 .

[238]  M. Jaggi,et al.  Therapeutic Applications of Curcumin Nanoformulations , 2015, The AAPS Journal.

[239]  O. H. Gonçalves,et al.  In vitro and in vivo evaluation of enzymatic and antioxidant activity, cytotoxicity and genotoxicity of curcumin-loaded solid dispersions. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[240]  Han Yang,et al.  Electrospray biodegradable microcapsules loaded with curcumin for drug delivery systems with high bioactivity , 2017 .

[241]  M. Jaggi,et al.  beta-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. , 2010, Colloids and surfaces. B, Biointerfaces.

[242]  Fazli Wahid,et al.  Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials , 2010, Archiv der Pharmazie.

[243]  Linqi Shi,et al.  Silver-Decorated Polymeric Micelles Combined with Curcumin for Enhanced Antibacterial Activity. , 2017, ACS applied materials & interfaces.

[244]  Kok-Gan Chan,et al.  Curcumin Nanoformulations for Colorectal Cancer: A Review , 2019, Front. Pharmacol..

[245]  M. M. Rizvi,et al.  Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice. , 2012, Biotechnology advances.

[246]  M. Krawczyk,et al.  Antidiabetic Activity of Curcumin: Insight Into Its Mechanisms of Action , 2018 .

[247]  G. Jagetia,et al.  Acceleration of wound repair by curcumin in the excision wound of mice exposed to different doses of fractionated γ radiation , 2012, International wound journal.

[248]  T. Maekawa,et al.  Curcumin Loaded-PLGA Nanoparticles Conjugated with Tet-1 Peptide for Potential Use in Alzheimer's Disease , 2012, PloS one.

[249]  M. Nouri,et al.  Nanocurcumin improves regulatory T-cell frequency and function in patients with multiple sclerosis , 2019, Journal of Neuroimmunology.

[250]  B. Aggarwal,et al.  Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. , 2009, The international journal of biochemistry & cell biology.

[251]  M. Boskabady,et al.  Anti‐inflammatory, antioxidant, and immunomodulatory effects of curcumin in ovalbumin‐sensitized rat , 2017, BioFactors.

[252]  R. Müller,et al.  Nanoparticles with decreasing surface hydrophobicities: influence on plasma protein adsorption. , 2000, International journal of pharmaceutics.

[253]  Yiqi Yang,et al.  Antimicrobial activity of wool fabric treated with curcumin , 2005 .

[254]  O. H. Gonçalves,et al.  Impact of curcumin nanoformulation on its antimicrobial activity , 2018 .

[255]  Zhaoliang Zhang,et al.  In situ injectable nano-composite hydrogel composed of curcumin, N,O-carboxymethyl chitosan and oxidized alginate for wound healing application. , 2012, International journal of pharmaceutics.