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研究生: 戴恕
Reddy, Desu Naveen Kumar
論文名稱: 薑黃素與薑黃素C3奈米粒子以甲殼素及不同莫耳比之α-, β-環糊精包覆複合體之研究
A comparative study of curcumin, curcumin C3 complex nanoparticles encapsulated with chitosan and different molar ratios of α- and β-cyclodextrin inclusion complexes
指導教授: 黃福永
Huang, Fu-Yung
學位類別: 博士
Doctor
系所名稱: 理學院 - 化學系
Department of Chemistry
論文出版年: 2020
畢業學年度: 108
語文別: 英文
論文頁數: 115
中文關鍵詞: 薑黃素-C環糊精殼聚醣奈米顆粒大腸桿菌金黃色葡萄球菌
外文關鍵詞: curcumin-C3, cyclodextrin, chitosan, nanoparticle, E. coli, S. aureus
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  • 薑黃粉中之黃色色素薑黃素具有多種生物活性,被廣泛應用在抗發炎、抗癌症、細菌性疾病之治療。其中之薑黃色素類物質去甲氧基薑黃素 (DMC) 與雙去甲氧基薑黃素 (BDMC) 雖不及薑黃素,亦具有生物活性。雖然薑黃素具有治療性質,但由於它的低溶解性與低生物利用度,無法取得許可於臨床上使用。為了解決此限制,薑黃素的奈米化與包覆複合體製備已有廣泛之應用。本研究中,以三種薑黃色素類物質為原料,製備成奈米粒以甲殼素奈米粒包覆以及薑黃素C3以不同比例之α, β-環糊精製成包覆複合體。這些複合體以核磁共振儀、傅立葉轉換紅外線光譜儀、X-射線繞射儀與穿透式電子顯微鏡鑑定其性質。在體外試驗中,薑黃素奈米粒與包覆複合體分別有90.4與97.8% 之誘捕效率。薑黃素C3奈米粒與包覆複合體都顯示有更佳之抗氧化活性以及對革蘭氏陽性與陰性菌之有較佳之生長抑制性。α, β-環糊精包覆複合體顯示為薑黃素較佳之載體,因此可應用於細菌感染之治療

    Curcumin, the bright yellow pigment of turmeric (Curcuma longa) possesses pleiotropic medicinal properties that have been widely used in the treatments of inflammatory diseases, cancer, bacterial diseases etc., Apart from curcumin, other curcumionoids, mainly demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) also show medicinal properties but not as effective as curcumin. Despite the therapeutic properties, curcumin and curcuminoids are not approved for clinical use due to its poor solubility and low bioavailability. To overcome this limitation, nanoparticles and inclusion complexes of curcumin are widely used. In this study, we used curcumin-C3 complex, a combination of all three curcuminoids as starting material and used two different approaches to test its effectiveness. Firstly, nanoparticles of curcumin and curcumin-C3 were prepared and then these nanoparticles were encapsulated in chitosan. Secondly, the curcumin and curcumin-C3 were combined with α and β-CD to form inclusion complexes using different molar ratios of cyclodextrins (1:1, 1:3, 1:5). These nanoparticles and inclusion complexes were characterized in both solid and solution forms by nuclear magnetic resonance, Fourier transform infrared spectroscopy, X-ray diffraction and transmission electron microscopy. The nanoparticles were characterized by nanoparticle tracking analysis. Additionally, in vitro assays using curcumin-C3 nanoparticles and inclusion complexes showed improved entrapment efficiency of 90.4% and 97.8% respectively. Our findings suggest that curcumin-C3 nanoparticle are effective than native curcumin. For inclusion complexes, α-CD at molar ratio 1:3 and 1:5 is suitable carrier for curcumin-C3. Compared to curcumin, curcumin-C3 shows more potency due to synergistic effect of three curcuminoids.

    Table of Contents Chinese Abstract (中文摘要) I Abstract II Acknowledgements V Table of Contents VI Contents of Tables X Contents of Figures XI Abbreviations List XIII Chapter 1: Research Background 1 1-1 History of Turmeric 1 1-2 Chemical properties of Curcumin 3 1-3 Medicinal properties of Curcumin 6 1-4 Therapeutic use of Curcumin 9 1-5 Limitations of Curcumin 10 1-6 Effective formulations of Curcumin 12 1-7 Pharmacological effects of Curcumin nanoformulations 16 1-8 Cyclodextrins (CDs) 18 1-9 Chitosan (CS) 21 1-10 Research objective 24 Chapter 2: Materials and Methods 25 2-1 Materials 25 2-2 Preparation of curcumin-C3 nanoparticles 25 2-3 Preparation of curcumin-C3 chitosan nanoparticles 26 2-4 Preparation of cyclodextrin inclusion complexes 27 2-5 UV-visible spectra 27 2-6 NMR spectroscopy 28 2-7 FT-IR analysis 28 2-8 Powder XRD 28 2-9 TEM 29 2-10 Nanoparticle Tracking Analysis 29 2-11 Entrapment efficiency and loading capacity of complexes 30 2-12 In vitro release studies 31 2-13 DPPH (2, 2’-diphenyl-1-picrylhydrazyl) assay 31 2-14 Minimal inhibitory concentration (MIC) 32 2-15 Antibacterial assay 33 2-16 Statistical analysis 33 Chapter 3: Results 35 3-1 Curcumin-C3 and curcumin encapsulated in chitosan nanoparticles 35 3-1-1 UV-spectral analysis of curcumin-C3-chitosan nanoparticles 35 3-1-2 FT-IR spectra of curcumin-C3-chitosan nanoparticles 36 3-1-3 XRD pattern of curcumin-C3-chitosan nanoparticles 37 3-1-4 Morphology studies of curcumin-C3-chitosan nanoparticles 37 3-1-5 Nanoparticle tracking analysis of curcumin-C3-chitosan nanoparticles 38 3-1-6 Entrapment efficiency and loading capacity 39 3-1-7 In vitro release studies from chitosan nanoparticles 39 3-1-8 Antioxidant activity of curcumin-C3-chitosan nanoparticles 40 3-1-9 Minimal inhibitory concentration of curcumin-C3-chitosan nanoparticles 40 3-1-10 Antibacterial activity of curcumin-C3-chitosan nanoparticles 41 3-2 Curcumin-C3 complexed to different molar ratios of α- and β-cyclodextrin 41 3-2-1 UV spectra of curcumin-C3 inclusion complexes 43 3-2-2 NMR spectra of curcumin-C3 inclusion complexes 45 3-2-3 FT-IR spectral analysis of curcumin-C3 inclusion complexes 45 3-2-4 XRD pattern analysis of curcumin-C3 inclusion complexes 47 3-2-5 Morphology studies using TEM for curcumin-C3 inclusion complexes 47 3-2-6 Entrapment efficiency of curcumin-C3 inclusion complexes 48 3-2-7 Antioxidant activity of curcumin-C3 inclusion complexes 48 3-2-8 Minimal inhibitory concentration of curcumin-C3 inclusion complexes 49 3-2-9 Antibacterial activity of curcumin-C3 inclusion complexes 49 Chapter 4: Discussion 51 4-1 Curcumin-C3 and curcumin encapsulated in chitosan nanoparticles 51 4-2 Curcumin-C3 and curcumin inclusion complexes 55 Chapter 5: Conclusion 59 References 61 Tables 78 Figures 83 Related Paper Publications 115

    Agashe, H., Sahoo, K., Lagisetty, P., and Awasthi, V. Cyclodextrin mediated entrapment of curcuminoid 4- [3,5-bis (2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] or CLEFMA in liposomes for treatment of xenograft lung tumor in rats. Colloids and Surfaces B: Biointerfaces 84, 329-337. 2011.

    Aggarwal, B. B., Yuan, W., Li, S., and Gupta, S. C. Curcumin free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Molecular Nutrition & Food Research 57, 1529-1542, 2013.

    Anand, P., Nair, H. B., Sung, B., Kunnumakkara, A. B., Yadav, V. R., and Tekmal, R. R. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochemical Pharmacology 79, 330-338, 2010.

    Azandeh, S. S., Abbaspour, M., Khodadadi, A., Khorsandia, L., Orazizadeha, M., and Heidari-Moghadam, A. Anticancer activity of curcumin-loaded PLGA nanoparticles on PC3 prostate cancer cells. Iranian Journal of Pharmaceutical Research 16 (3), 868-879, 2017.

    Bansal, S., and Chhibber, S. Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055- induced lung infection in BALB/c mice. Journal of Medical Microbiology 59(4), 429-437, 2010.

    Bar, R., and Ulitzur, S. Bacterial toxicity of cyclodextrins: luminuous Escherichia coli as a model. Applied Microbiology and Biotechnology 41(5), 574-577, 1994.

    Bhawana, Basniwal, R. K., Buttar, H. S., Jain, V. K., and Jain, N. Curcumin nanoparticles: Preparation, characterization, and antimicrobial study Journal of Agricultural and Food Chemistry 59, 2056–2061, 2011.

    Biswas, S. K. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox. Oxidative Medicine and Cellular Longevity. 5698931, 2016.

    Bomdyal, R. S., Shah, M. U., Doshi, Y. S., Shah, V. A., and Khirade, S. P. Antibacterial activity of curcumin (turmeric) against periopathogens - An in vitro evaluation. Journal of Advanced Clinical & Research Insights 4, 175–180, 2017.

    Carvalho, A. C., Gomes, A. C., Pereira-Wilson, C., and Lima, C. F. Mechanisms of action of curcumin on aging: Nutritional and pharmacological applications. Chapter 35. Molecular basis of nutrition and aging: A volume in the molecular nutrition series. 491-511, 2016.

    Carneiro, S. B., Duarte, F. I. C., Heimfarth, L., Quintans, J. S. S., Quintans-Júnior, L. J., Veiga Júnior, V. F., and de Lima, A. A. N. Cyclodextrin–drug inclusion complexes: In vivo and in vitro approaches. International Journal of Molecular Sciences 20(3), 642-664, 2019.

    Chen, C. Y., Yang, W. L., and Kuo, S. Y. Cytotoxic activity and cell cycle analysis of hexahydrocurcumin on SW 480 human colorectal cancer cells. Natural Product Communications 6, 1671-1672, 2011.

    Chauhan, P., Tamrakar, A. K., Mahajan, S., and Prasad, G.B.K.S. Chitosan encapsulated nanocurcumin induces GLUT-4 translocation and exhibits enhanced anti-hyperglycemic function. Life Sciences 213, 226–235, 2018.

    Cheirsilp, B., and Rakmai, J. Inclusion complex formation of cyclodextrin with its guest and their applications. Biology, Engineering and Medicine 2(1), 1-6, 2016.

    Chen, H., Wu, J., Sun, M.; Guo, C., Yu, A., and Cao, F. N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin. Journal of Liposome Research 22,100-109, 2012.

    Chen, J., Qin, X., Zhong, S., Chen, S., Su, W., and Liu, Y. Characterization of curcumin/cyclodextrin polymer inclusion complex and investigation on its antioxidant and antiproliferative activities. Molecules 23(5), 1179-1191, 2018.

    Chuah L.H., Billa, N., Roberts, C. J., Burley, J.C., and Manickam, S. Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon. Pharmaceutical Development and Technology 18 (3), 591-599, 2013.

    Cridge, B. J., Larsen, L., and Rosengren, R. J. Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers. Oncology Discovery 1(1), 6-14, 2013.

    Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh, D. F.H., Javanmard, R., Dokhani, A., Khorasany, S., and Mozafari, M.R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2), E57, 2018.

    Dandawate, P. R., Vyas, A., Ahmad, A., Banerjee, S., Deshpande, J., Swamy, K. V., Jamadar, A., Dumhe-Klaire, A. C., Padhye, S., and Sarkar, F. H. Inclusion complex of novel curcumin analogue CDF and β-cyclodextrin (1:2) and its enhanced in vivo anticancer activity against pancreatic cancer. Pharmaceutical Research 29(7), 1775-86, 2012.

    Darandale, SS., and Vavia, PR. Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. Journal of Inclusion Phenomena and Macrocyclic Chemistry 75, 315-22, 2013

    Das, RK., Kasoju, N., Bora, U., Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine 6, 153-160, 2010

    De, R., Kundu, P., Swarnakar, S., Ramamurthy, T., Chowdhury, A., Nair, GB., and Mukhopadhyay, AK., Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrobial Agents and Chemotherapy 53(4), 1592-1597, 2009.

    Doggui, S., Sahni, J. K., Arseneault, M., Dao, L., and Ramassamy, C. Neuronal uptake and neuroprotective effect of curcumin loaded PLGA nanoparticles on the human SK-N-SH cell line. Journal of Alzheimer's Disease 30, 377-392, 2012.

    Dovigo, L.N., Carmello, J.C., de Souza Costa, C.A., Vergani, C.E., Brunetti, I.L., and Bagnato, V.S. Curcumin-mediated photodynamic inactivation of Candida albicans in a murine model of oral candidiasis. Medical Mycology 51, 243-51, 2013.

    Dua, K., Bebawy, M., Awasthi, R., Tekade, R.K., Tekade, M., Gupta, G., De Jesus Andreoli Pinto, T., and Hansbro, P.M. Application of chitosan and its derivatives in nanocarrier based pulmonary drug delivery systems. Pharmaceutical Nanotechnology. 5(4), 243-249, 2017.

    Duarte, V. M., Han, E., Veena, M. S., Salvado, A., Suh, J. D., and Liang, L. J. Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKbeta protein of the NFkappaB pathway. Molecular Cancer Therapeutics 9, 2665-2675, 2010.

    Edwards, R. L., Luis, P. B., Varuzza, P. V., Joseph, A. I., Presley, S. H., Chaturvedi, R., and Schneider, C. The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. Journal of Biological Chemistry 292(52), 21243-21252, 2017.

    El-Rahman, S. N. A., and Al-Jameel, S. S. Protection of curcumin and curcumin nanoparticles against cisplatin induced nephrotoxicity in male rats. Sch. Acad. Journal of Biosciences 2(3), 214-223, 2014.

    Feuangthit, NS., Chawanphat, M., Wuttinont, T., Pornchai, R., and Pranee, R. Enhanced cytotoxic, antioxidant and anti-inflammatory activities of curcumin diethyl disuccinate using chitosan-tripolyphosphate nanoparticles. Journal of Drug Delivery Science and Technology 53, ID 101118, 2019.

    Frenkel, K. Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacology & Therapeutics 53,127-166, 1992.

    Foged, C., Brodin, B., Frokjaer, S., and Sundblad, A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. International Journal of Pharmaceutics 298, 315-22, 2005.

    Geng, Y. A., Dalhaimer, P., Cai, S., Tsai, R., Tewari, M., Minko, T., and Discher, D. E. Shape effects of filaments versus spherical particles in flow and drug delivery. Nature Nanotechnology 2, 249-55, 2007.

    Gera, M., Kumar, R., Jain, V. K., and Suman. Preparation of a Novel Nanocurcumin Loaded Drug Releasing Medicated Patch with Enhanced Bioactivity against Microbes. Advanced Science, Engineering and Medicine 7, 485-91, 2015.

    Gera, M., Sharma, N., Ghosh, M., Huynh, D.L., Lee, S.J., Min, T., Kwon, T., and Jeong, D.K. Nanoformulations of curcumin: an emerging paradigm for improved remedial application. Oncotarget 8(39), 66680-66698, 2017.

    Gonil, P. P., Warayuth Sajomsang, W., Ruktanonchai, U. R., Pimpha, N., Sramala, I., Nuchuchua, O., Saesoo, S., Chaleawlert-umpon, S., and Puttipipatkhachorn. S. Novel quaternized chitosan containing β-cyclodextrin moiety: Synthesis, characterization and antimicrobial activity. Carbohydrate Polymers 83(2), 905-913, 2011.

    González-Reyes, S., Guzmán-Beltrán, S., Medina-Campos, O.N., and Pedraza-Chaverri, J. Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats. Oxidative Medicine and Cellular Longevity ID 801418, 2013.

    Gottenbos, B., Grijpma, DW., van der Mei, HC., Feijen, J., and Busscher HJ. Antimicrobial effects of positively charged surfaces on adhering Gram-positive and Gram-negative bacteria. Journal of Antimicrobial Chemotherapy 48(1), 7-13, 2001.

    Gou, M., Men, K., Shi, H., Xiang, M., Zhang, J., and Song, J., Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale. 3, 1558-67, 2011.

    Goy, R. C., Morais, S. T.B., and Assis, O. B. G. Evaluation of the antimicrobial activity of chitosan and its quaternized derivative on E. coli and S. aureus growth. Revista Brasileira de Farmacognosia 26, 122-127, 2016.

    Gupta, A., Mahajan, S., and Sharma, R. Evaluation of antimicrobial activity of Curcuma longa rhizome extract against Staphylococcus aureus. Biotechnology Reports 6, 51-55, 2015.

    Gupta, S. C., Patchva, S., Koh, W., and Aggarwal, B. B. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clinical and Experimental Pharmacology and Physiology 39(3), 283-99, 2012.

    Guzman-Villanueva, D., El-Sherbiny, I. M., Herrera-Ruiz, D., and Smyth, H. D. Design and in vitro evaluation of a new nanomicroparticulate system for enhanced aqueous-phase solubility of curcumin. BioMed Research International ID 724763. 2013.

    Harada, T., Pham, D.T., Leung, M. H., Ngo, H. T., Lincoln, S. F., Easton, C. J., and Kee, T. W. Cooperative binding and stabilization of the medicinal pigment curcumin by diamide linked γ-cyclodextrin dimers: a spectroscopic characterization. The Journal of Physical Chemistry B 115(5), 1268-74, 2011.

    Hattori-Nakakuki, Y., Nishigori, C., Okamoto, K., Imamura, S., Hiai, H., and Toyokuni, S. Formation of 8-hydroxy-2′-deoxyguanosine in epidermis of hairless mice exposed to near-UV. Biochemical and Biophysical Research Communications 201, 1132-1139,1994

    Hejazi, R., and Amiji, M. Chitosan-Based Delivery Systems: Physicochemical Properties and Pharmaceutical Applications. Chapter 10, Polymeric Biomaterials, Revised and Expanded, 213-218. 2001.

    Herman, F., Westfall, S., Brathwaite, J., and Pasinetti, G. M. Suppression of presymptomatic oxidative stress and inflammation in neurodegeneration by grape-derived polyphenols. Frontiers in Pharmacology 9, 867-886, 2018.

    Hewlings, S. J., and Kalman, D. S. Curcumin: A Review of its' effects on human health. Foods. 6(10), 92-102, 2017.

    Ireson, C., Orr, S., Jones, D. J., Verschoyle, R., and Lim, C. K.; Luo, J. L. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Research. 61,1058-64, 2001.

    Islam, A., Rebello, L., and Chepyala, S. Review on nanoformulations of curcumin (Curcuma longa Linn.): Special emphasis on Nanocurcumin®. International Journal of Nature and Life Sciences 3(1), 1-12, 2019.

    Ja'far, M. H., Kamal, N. S. N. M., Boon, H., Kamaruzzaman, M. F., Zain, N. M., Noorfatimah, Y., and Muggundha, R. Inclusion of curcumin in β-cyclodextrins as potential drug delivery system: Preparation, characterization and its preliminary cytotoxicity approaches. Sains Malaysiana 47, 977-989, 2018.

    Jagetia, G.C., and Rajanikant, G.K. Curcumin stimulates the antioxidant mechanisms in mouse skin exposed to fractionated γ-irradiation. Antioxidants 4, 25-41, 2015.

    Jahromi, M. A. M., Al-Musawi, S., Pirestani, M., Ramandi, M. F., Rajayi, H., Hassan, Z. M., Kamali, M., and Mirnejad, R. Curcumin-loaded chitosan tripolyphosphate nanoparticles as a safe, natural and effective antibiotic inhibits the infection of Staphylococcus aureus and Pseudomonas aeruginosa in vivo. Iranian Journal of Biotechnology 12(3), e1012, 2014.

    Jiang, H., Li, ZP., Tian, GX., Pan, RY., Xu, CM., Zhang, B., and Wu, J.L. Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects. International Journal of Nanomedicine 14, 1789-1804, 2019.

    Joe, B., and Lokesh, B. R. Role of capsaicin, curcumin and dietary n—3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochimica et Biophysica Acta 1224, 255-263, 1994.

    Jurenka, J. S. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alternative medicine review: a journal of clinical therapeutic 14, 141-153, 2009.

    Khalil, N. M., do Nascimento, T. C., Casa, D. M., Dalmolin, L. F., de Mattos, A. C., and Hoss, I. Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats. Colloids and Surfaces B: Biointerfaces 101, 353-360, 2013.

    Khan, M. A., Zafarya, M., Mehdi, S. H., Ahmad, I. M., and Rizvi, M. A. Characterization and anti-proliferative activity of curcumin loaded chitosan nanoparticles in cervical cancer. International Journal of Biological Macromolecules 93, 242-253, 2016.

    Kim, T. H., Jiang, H. H., Youn, Y. S., Park, C. W., Tak, K. K., and Lee, S. Preparation and characterization of water-soluble albuminbound curcumin nanoparticles with improved antitumor activity. International Journal of Pharmaceutics 403, 285-291, 2011.

    Kiuchi, F., Goto, Y., Sugimoto, N., Akao, N.; Kondo, K., and Tsuda, Y. Nematocidal activity of turmeric: synergistic action of curcuminoids. Chemical and Pharmaceutical Bulletin 41,1640e3, 1993.

    Kumar, A., Ahuja, A., Ali, J., and Baboota, S. Curcumin loaded nano globules for solubility enhancement: preparation, characterization and ex vivo release study. Journal of Nanoscience and Nanotechnology 12, 8293-8302, 2012.

    Kumari, S., and Rath, P. K. Extraction and characterization of chitin and chitosan from (Labe rohit) fish scales. Procedia Materials Science 6, 482-489, 2014.

    Kong, M., Chen, X. G., Xing, K., and Park, H. J. Antimicrobial properties of chitosan and mode of action: a state-of-the-art review. International Journal of Food Microbiology 144(1), 51-63, 2010.

    Lai, C. S., Wu, J. C., Yu, S. F., Badmaev, V., Nagabhushanam, K., and Ho, C. T. Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis. Molecular Nutrition & Food Research 55(18), 19-28, 2011.

    Lal, J. Turmeric, curcumin and our life: A review Bulletin of Environment, Pharmacology and Life Sciences 1 (7), 11-17, 2012.

    Larasati, Y.A., Yoneda-Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., and Kato, J-Y. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Scientific Reports 8, 2039-2042, 2018.

    Lee, W. H., Loo, C. Y., Bebawy, M., Luk, F., Mason, R. S., and Rohanizadeh, R. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Current Neuropharmacology 11(4), 338-378, 2013.

    Li, C., Zhang, Y., Su, T., Feng, L., Long, Y., and Chen, Z. Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin. International Journal of Nanomedicine 7, 5995-6002, 2012.

    Liao, J. H., Wu, T. H., Chen, M. Y., Chen, W. T., Lu, S. Y., Wang, Y. H., Wang, S. P., Hsu, Y. M., Huang, Y. S., Huang, Z. Y., Lin, Y. C., Chang, C. M., Huang, F. Y., and Wu, S. H. The comparative studies of binding activity of curcumin and didemethylated curcumin with selenite: Hydrogen bonding vs acid-base interactions. Scientific Reports 5, 17614-17625, 2015.

    Liao, J. H., Huang, Y. S., Lin, Y. C., Huang, F. Y., Wu, S. H., and Wu, T. H. Anticataractogenesis mechanisms of curcumin and a comparison of its degradation products: An in vitro study. Journal of Agricultural and Food Chemistry 64(10), 2080-2086, 2016.

    Lin, X., Bai, D., Wei, Z., Zhang, Y., Huang, Y., Deng, H., and Huang, X. Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. PLOS One 14(5), e0216711, 2019.

    Loftsson, T., Jarho, P., Másson, M., and Järvinen, T. Cyclodextrins in drug delivery. Expert Opinion on Drug Delivery 2(2), 335-351, 2002.

    Lüer, S., Troller, R., and Aebi, C. Antibacterial and anti-inflammatory kinetics of curcumin as a potential antimucositis agent in cancer patients. Nutrition and Cancer 64, 975–981, 2012.

    Luo, J., and Yang, M. Demethoxycurcumin: a potential antimicrobial agent. Journal of Thermal Analysis and Calorimetry 115(3), 2331–2338, 2013.

    Mandroli, P. S., and Bhat, K. An in-vitro evaluation of antibacterial activity of curcumin against common endodontic bacteria. Journal of Applied Pharmaceutical Science 3(10), 106-108, 2013.

    Mangolim, C. S., Moriwaki, C., Nogueira, A., C, Sato., F, Baesso, M. L., Neto, A. M., and Matioli, G. Curcumin-β-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chemistry 153, 361-370, 2014.

    Maria, D. N., Mishra, S. R., Wang, L., Abd-Elgawad, A. H., Soliman, O. A., El-Dahan, M. S., and Jablonski, M. M. Water-soluble complex of curcumin with cyclodextrins: Enhanced physical properties for ocular drug delivery. Current Drug Delivery 14(6), 875-886, 2017.

    Marcolino, V. A., Zanin, G. M., Durrant, L. R., Benassi Mde, T., and Matioli, G. Interaction of curcumin and bixin with β-cyclodextrin: complexation methods, stability, and applications in food. Journal of Agricultural and Food Chemistry 59(7), 3348-3357, 2011.

    Marquardt, J.U., Gomez-Quiroz, L., Arreguin Camacho, L.O., Pinna, F., Lee, Y.H., Kitade, M., Domínguez, M.P., Castven, D.; Breuhahn, K., Conner, E.A., Galle, P.R., Andersen, J.B., Factor, V. M., and Thorgeirsson, S. S. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. Journal of Hepatology 63(3), 661-669, 2015.

    Mazzarino, L., Travelet, C., Ortega-Murillo, S., Otsuka, I., Pignot-Paintrand, I., Lemos-Senna, E., and Borsali. R. Elaboration of chitosan-coated nanoparticles loaded with curcumin for mucoadhesive applications. Journal of Colloid and Interface Science 370, 58-66, 2012.

    Mishra, B., Priyadarsini, I. K., Bhide, M. K., Kadam, R. M., and Mohan, H. Reactions of superoxide radicals with curcumin: probable mechanisms by optical spectroscopy and EPR. Free Radical Research 38, 355-362, 2004.

    Mohan, P. R. K., Sreelakshmi, G., Muraleedharan, C. V., and Roy, J. Water soluble complexes of curcumin with cyclodextrins: Characterization by FT-Raman spectroscopy. Vibrational Spectroscopy 62, 77-84, 2012.

    Moreillon, J. J., Bowden, R. G., Deike. E., Griggs. J., Wilson. R., Shelmadine. B., Cooke. M., and Beaujean. A. The use of an antiinflammatory supplement in patients with chronic kidney disease. Journal of Complementary and Integrative Medicine 10, 143-152, 2013.

    Mourtas, S., Canovi, M., Zona, C., Aurilia, D., Niarakis, A., and La Ferla, B. Curcumin-decorated nanoliposomes with very high affinity for amyloid-beta1-42 peptide. Biomaterials 32, 1635-45. 2011.

    Murakami, A., Furukawa, I., Miyamoto, S., Tanaka, T., and Ohigashi, H. Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis. Biofactors 39, 221-232, 2013.

    Nair, R. S., Morris, A., Billa, N., and Leong, C. O. An evaluation of curcumin-encapsulated chitosan nanoparticles for transdermal delivery. AAPS PharmSciTech 20(2), 69, 2019.

    Nguyen, M. H., Yu, H., Kiew, T. Y., and Hadinoto, K. Cost-effective alternative to nano-encapsulation: Amorphous curcumin–chitosan nanoparticle complex exhibiting high payload and supersaturation generation. European Journal of Pharmaceutics and Biopharmaceutics 96, 1-10, 2015.

    Okada, K., Wangpoengtrakul, C., Tanaka, T., Toyokuni, S., Uchida K., and Osawa T. Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice. Journal of Nutrition 131, 2090-2095, 2001.

    Olivera, A., Moore, T. W., Hu, F., Brown, A.P., Sun, A., Liotta, D. C., Snyder, J.P., Yoon, Y., Shim, H., Marcus, A.I., Miller, A.H., and Pace, T.W. Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties. International Immunopharmacology 12(2), 368-377, 2012.

    O'Toole, M. G., Soucy, P. A., Chauhan, R., Raju, M. V., Patel, D. N., Nunn, B. N., Keynton, M. A., Ehringer, W. D., Nantz, M. H., Keynton, R. S, and Gobin, A.S. Release-modulated antioxidant activity of a composite curcumin-chitosan polymer. Biomacromolecules 17(4), 1253-1260, 2016.

    Pan, M. H., Huang, T. M., and Lin, J. K. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metabolism and Disposition 27(4), 486-494, 1999.

    Pandit, R. S., Gaikwad, S. C., Agarkar, G. A., Gade, A. K., and Rai, M. Curcumin nanoparticles: physico-chemical fabrication and it’s in vitro efficacy against human pathogens. 3 Biotech 5, 991-997, 2015.

    Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Atkin, S.L., Majeed, M., and Sahebkar, A. Curcuminoids plus piperine modulate adipokines in type 2 diabetes mellitus. Current Clinical Pharmacology 12(4), 253-258, 2017.

    Panahi, Y., Kianpour, P., Mohtashami, R., Jafari, R., Simental-Mendía, L. E., and Sahebkar, A. Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: A randomized controlled trial. Drug Research (formerly Arzneimittelforschung) 67(4), 244-251, 2017.

    Pathak, L., Kanwal, A., and Agrawal, Y., Curcumin loaded self-assembled lipid-biopolymer nanoparticles for functional food applications. Journal of Food Science and Technology 52(10), 6143-6156, 2015.

    Perkins, S., Verschoyle, R. D., Hill, K., Parveen, I., Threadgill, M. D., Sharma, R. A., Williams, M. L., Steward, W. P., and Gescher, A. J. Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiology, Biomarkers & Prevention 11(6), 535-540, 2002.

    Phillips, J., Moore-Medlin, T., Sonavane, K., Ekshyyan, O., McLarty, J., and Nathan, C. A. Curcumin inhibits UV radiation-induced skin cancer in SKH-1 mice. Otolaryngology–Head and Neck Surgery 148, 797-803, 2013.

    Prasad, S., Tyagi, A. K., and Aggarwal, B. B. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Research and Treatment 46(1), 2-18, 2014.

    Prasad, S., Gupta, S. C., Tyagi, A. K., and Aggarwal, B. B. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnology Advances 32, 1053-1064, 2014.

    Prasad, S., and Aggarwal, B. B. Turmeric, the golden spice: From traditional medicine to modern medicine. Chapter 13. Herbal medicine: Biomolecular and Clinical Aspects. 2nd edition. CRC Press/Taylor & Francis, 2011.

    Priyadarsini, K. I. Chemical and structural features influencing the biological activity of curcumin. Current Pharmaceutical Design 19, 2093100. 2013.

    Popat, A., Karmakar. S., Jambhrunkar, S., Xu, C., and Yu, C. Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity. Colloids and Surfaces B: Biointerfaces 117, 520-527, 2014.

    Queiroz, M. F., Melo, R. T., Sabry, D. A., Sassaki, G. L., and Rocha, H. A. O. Does the use of chitosan contribute to oxalate kidney stone formation? Marine Drugs 13, 141-158, 2015.

    Rachmawati, H., Edityaningrum, CA., and Mauludin, R. Molecular inclusion complex of curcumin-beta-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel. AAPS PharmSciTech. 14, 1303-1312. 2013.

    Radjaram, A., Hafid, A. F., and Setyawan, D. Dissolution enhancement of curcumin by hydroxypropyl-β-cyclodextrin complexation. International Journal of Pharmacy and Pharmaceutical Sciences 5, 401-405. 2013.

    Rahmani, A. H., Alsahli, M. A., Aly, S. M., Khan, M. A., and Aldebasi, Y. H. Role of curcumin in disease prevention and treatment. Advanced Biomedical Research 28, 38, 2018.

    Rajitha, B., Nagaraju, G. P., Shaib, W. L., Alese, O. B., Snyder, J. P., Shoji, M., Pattnaik, S., Alam, A., and El-Rayes, B. F. Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer. Molecular Carcinogenesis 56, 288-299, 2017.

    Rajan, M., and Raj, V. Encapsulation, characterisation and in-vitro release of anti-tuberculosis drug using chitosan - poly ethylene glycol nanoparticles. International Journal of Pharmacy and Pharmaceutical Sciences 4, 255-259, 2012.

    Ravindranath, V., and Chandrasekhara, N. In vitro studies on the intestinal absorption of curcumin in rats. Toxicology 20, 251-257. 1981.

    Rezaei, M., Oryan, S., Nourani, M.R., Mofid, M., and Mozafari, M. Curcumin nanoparticle-incorporated collagen/chitosan scaffolds for enhanced wound healing. Bioinspired Biomimetic and Nanobiomaterials 7, 159-166, 2018.

    Rezaei, M., Oryan, S., and Javeri, A. Curcumin nanoparticles incorporated collagen-chitosan scaffold promotes cutaneous wound healing through regulation of TGF-β1/Smad7 gene expression. Materials Science and Engineering C: Materials for Biological Applications 98, 347-357, 2019.

    Ryan, J. L., Heckler, C. E., Ling, M., Katz, A., Williams, J. P., and Pentland, A. P. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiation Research 180, 34-43, 2013.

    Sahebkar, A., Maria-Corina, S., Ursoniu, S., and Banach, M. Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Journal of Functional Foods 18, 898-909, 2015.

    Sandur, S. K., Pandey, M. K., Sung, B., Ahn, K. S., Murakami, A., and Sethi, G. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 28, 1765e73. 2007.

    Sasaki, H., Sunagawa, Y., Takahashi, K., Imaizumi, A., Fukuda, H., and Hashimoto, T. Innovative preparation of curcumin for improved oral bioavailability. Biological and Pharmaceutical Bulletin 34, 660-665. 2011.

    Sharma, R. A., Euden, S. A., Platton, S. L., Cooke, D. N., Shafayat, A., Hewitt, H. R., Marczylo, T. H., Morgan, B., Hemingway, D., Plummer, S. M., Pirmohamed, M., Gescher, A. J., and Steward, W. P. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clinical Cancer Research 10, 6847-6854, 2004.

    Sharma, G., Valenta, D. T., Altman, Y., Harvey, S., Xie, H., Mitragotri, S., and Smith, J. W. Polymer particle shape independently influences binding and internalization by macrophages. The Journal of Controlled Release 147, 408-412, 2010.

    Sharma, M., Manoharlal, R., Puri, N., and Prasad, R. Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Bioscience Reports 30, 391-404. 2010.

    Shi, H. S., Gao, X., Li, D., Zhang, Q. W., Wang, Y. S., and Zheng, Y. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation. International Journal of Nanomedicine 7, 2601-2611, 2012.

    Shishodia, S. Molecular mechanisms of curcumin action: gene expression. Biofactors 39, 3755. 2013.

    Shinde Patil, V. R., Campbell, C. J., Yun, Y. H., Slack, S. M., and Goetz, D. J. Particle diameter influences adhesion under flow. The Biophysical Journal 80, 1733-1743, 2001.

    Shlar, I., Droby, S., Choudhary, R., and Rodov, V. The mode of antimicrobial action of curcumin depends on the delivery system: monolithic nanoparticles vs. supramolecular inclusion complex. RSC Advances 7, 42559, 2017.

    Sierpe, R., Lang, E., Jara, P., Guerrero, A. R., Chornik, B., Kogan, M. J., and Yutronic, N. Gold nanoparticles interacting with β-cyclodextrin-phenylethylamine inclusion complex: a ternary system for photothermal drug release. ACS Applied Materials & Interfaces 7,15177-15188, 2015.

    Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., and Srinivas, P. S. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica 64, 353-356, 1998.

    Singh, R. P., and Jain, D.A. Evaluation of antimicrobial activity of curcuminoids isolated from turmeric. International Journal of Pharmaceutical and Life Sciences 3, 1368-1376, 2012.

    Singh, P.K., Wani, K., Kaul-Ghanekar., R. Prabhune, A., and Ogale, S. From micron to nano-curcumin by sophorolipid co-processing: highly enhanced bioavailability, fluorescence, and anti-cancer efficacy. RSC Advances 4, 60334, 2014.

    Singh, R., Bharti, N., Madan, J., and Hiremath, S. N. Characterization of cyclodextrin inclusion complexes – A review. Journal of Pharmaceutical Science and Technology 2, 171-183, 2010.

    Singh, R. K., Rai, D., Yadav, D., Bhargava, A., Balzarini, J., and Clercq, E. D. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid. European Journal of Medicinal Chemistry 45, 1078-1086, 2010.

    Stanić, Z. Curcumin, a compound from natural sources, a true scientific challenge - A review. Plant Foods for Human Nutrition 72, 1-12, 2017.

    Sukandar, E. Y., Kurniati, N. F., Puspatriani, K., and Adityas, H. P. Antibacterial activity of curcumin in combination with tetracycline against Staphylococcus aureus by disruption of cell wall. Journal of Medicinal Plants Research 12, 1-8, 2018.

    Sun, J., Zhao, Y., and Hu, J. Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One 8, e67078. 2013.

    Suresh, D., and Srinivasan, K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian Journal of Medical Research 131, 682-691, 2010.

    Takahashi, M., Suzuki, K., Kim, H. K., Otsuka, Y., Imaizumi, A., and Miyashita, M. Effects of curcumin supplementation on exercise-induced oxidative stress in humans. International Journal of Sports Medicine 35, 469-475, 2014.

    Takahashi, M., Uechi, S., Takara, K., Asikin, Y., and Wada, K. Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. Journal of Agricultural and Food Chemistry 57, 9141-9146, 2009.

    Tanvir, E. M., Hossen, S. M., Hossain, F. M., Afroz, R., Gan S. H. M., Khalil, I., and Karim. N. Antioxidant properties of popular turmeric (Curcuma longa) varieties from Bangladesh. Journal of Food Quality, ID 8471785, 2017.

    Terlecky, S. R., Terlecky, L. J., and Giordano, C. R. Peroxisomes, oxidative stress, and inflammation. World Journal of Biological Chemistry 26, 93-97, 2012.

    Teow, S. Y., Liew, K., Ali, S., A, Khoo, A. S., Peh, S. C. Antibacterial action of curcumin against Staphylococcus aureus: A brief review. Journal of Tropical Medicine 10, 1-10, 2016.

    Tyagi, P., Singh, M., Kumari, H., Kumari, A., and Mukhopadhyay, K. Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS ONE 10, e0121313, 2017.

    Tyagi, S., and Farooqi J. A. Curcumin nanoformulations as potential antimicrobial agent. Journal of Bacteriology & Mycology 5(5), 378‒379, 2017.

    Vajragupta, O., Boonchoong, P., Watanabe, H., Tohda, M., Kummasud, N., and Sumanont, Y. Manganese complexes of curcumin and its derivatives: evaluation for the radical scavenging ability and neuroprotective activity. Free Radical Biology and Medicine 35, 1632-1644, 2003.

    Vimala, K., Mohan, Y. M., Sivudu, K. S., Varaprasad, K., Ravindra, S., Reddy, N. N., Padma, Y., Sreedhar, B., and Raju, M. K. Fabrication of porous chitosan films impregnated with silver nanoparticles: a facile approach for superior antibacterial application. Colloids and Surfaces B: Biointerfaces 76, 248-258, 2010.

    Wang, Q. Z., Chen, X. G., Liu, N., Wang, S. X., Liu, C. S., Meng, X. H., and Liu, C. G. Protonation constants of chitosan with different molecular weight and degree of deacetylation. Carbohydrate Polymers 65, 194-201, 2006.

    Wang, Y., Lu, Z., Wu, H., and Lv, F. Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens. International Journal of Food Microbiology 136(1), 71-74, 2009.

    Wang, J., Zhou, X. Li., W. Deng, X., Deng Y., and Niu X. Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process of α-hemolysin. Scientific Reports 6, 28254. 2016.

    Wang, X-S., Zhang, Z-R., Zhang, M-M., Sun, M-X., Wang, W-W., and Xie, C-L. Neuroprotective properties of curcumin in toxin-base animal models of Parkinson’s disease: a systematic experiment literatures review. BMC Complementary Medicine and Therapies 17, 412. 2017.

    Wahlstrom, B. and Blennow, G. A study on the fate of curcumin in the rat. Acta Pharmacologica et Toxicologica (Copenh) 43, 86-92, 1978.

    Weitzman, S.A., and Gordon, L.I. Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood 76, 655-663, 1990.

    Wong, K. E., Ngai, S. C., Chan, K-G., Lee, L-H., Goh, B-H., and Chuah, L-H. Curcumin nanoformulations for colorectal cancer: A review. Frontiers in Pharmacology 10, 152, 2019.

    Xie, X., Tao, Q., Zou, Y., Zhang, F., Guo, M., and Wang, Y. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms. Journal of Agricultural and Food Chemistry 59, 9280-9289, 2011.

    Yadav, V. R., Prasad, S., Kannappan, R., Ravindran, J., Chaturvedi, M. M., and Vaahtera, L. Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake. Biochemical Pharmacology 80, 1021-1032, 2010.

    Yadav, P., Bandyopadhyay, A., Chakraborty, A., and Sarkar. K. Enhancement of anticancer activity and drug delivery of chitosan-curcumin nanoparticle via molecular docking and simulation analysis. Carbohydrate Polymers 182, 188–198, 2018.

    Yallapu, M. M., Jaggi, M., and Chauhan, S. C. Poly(β-cyclodextrin)/curcumin self-assembly: a novel approach to improve curcumin delivery and its therapeutic efficacy in prostate cancer cells. Macromolecular Bioscience 10(10),1141-1151, 2010.

    Zemljič, L., Julija, V., Tijana, R., Matej, B., Olivera, S., and Tatjana, K. Antimicrobial and antioxidant functionalization of viscose fabric using chitosan-curcumin formulations. Textile Research Journal 84(3), 2014.

    Zhang, L., Man, S., Qiu, H., Liu, Z., Zhang, M., Ma, L., and Gao, W. Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin. Environmental Toxicology and Pharmacology 48, 31-38, 2016.

    Zhou, H., Beevers, C. S., and Huang, S. Targets of curcumin. Current Drug Targets 12(3), 332-347, 2011.

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