Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability
Author(s)
R. Ravichandran*
ABSTRACT
Curcumin, a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of Curcumin in inflammatory disorders, cardiovascular disease, cancer, Alzheimer’s disease and neurological disorders have been shown. However, the clinical application of Curcumin is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based drug delivery systems for Curcumin including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanoemulsions, complexes and dendrimer/dimer, have been attempted to enhance the oral bioavailability, biological activity or tissue-targeting ability of Curcumin. We attempted the nanosuspensions based delivery of curcumin. Nanonisation renders curcumin completely dispersible in aqueous media. To enhance the curcumin absorption by oral administration, nanoparticulate solid oral formulation of curcumin was prepared by us and the resulting capsule was then examined for its efficiency on bioavailability in Male Wistar rats at a dose of 100 mg curcumin/kg body weight and the pharmacokinetic parameters were compared to those of normal curcumin powder and a commercial curcumin capsule CUR-500. The bio-distribution of curcumin in organs of rat was also studied. Nanoparticulation significantly raised the curcumin concentration in selective organs in the body. The results obtained provide promising results for nanoparticulate Curcumin to improve its biological activities. Enhanced bioavailability of curcumin in the form of nanoparticle is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease. The available information also strongly suggests that nano-formulation of ingredients such as curcumin may be used as a novel nutrient delivery system too.
Cite this paper
R. Ravichandran, "Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability," Journal of Biomaterials and Nanobiotechnology, Vol. 4 No. 3, 2013, pp. 291-299. doi: 10.4236/jbnb.2013.43037.
R. Ravichandran, "Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability," Journal of Biomaterials and Nanobiotechnology, Vol. 4 No. 3, 2013, pp. 291-299. doi: 10.4236/jbnb.2013.43037.
References
[1] B. B. Aggarwal, A. Kumar and A. C. Bharti, “Anticancer Potential of Curcumin: Preclinical and Clinical Studies,” Anticancer Research, Vol. 23, No. 1A, 2003, pp. 363-398. [2] O. P. Sharma, “Antioxidant Activity of Curcumin and Related Compounds,” Biochemical Pharmacology, Vol. 25, No. 15, 1976, pp. 1811-1812. doi:10.1016/0006-2952(76)90421-4 [3] A. J. Ruby, G. Kuttan, K. D. Babu, K. N. Rajasekharan and R. Kuttan, “Anti-Tumour and Antioxidant Activity of Natural Curcuminoids,” Cancer Letters, Vol. 94, No. 1, 1995, pp. 79-83. doi:10.1016/0304-3835(95)03827-J [4] Y. Sugiyama, S. Kawakishi and T. Osawa, “Involvement of the Diketone Moiety in the Antioxidative Mechanism of Tetrahydrocurcumin,” Biochemical Pharmacology, Vol. 52, No. 4, 1996, pp. 519-525. doi:10.1016/0006-2952(96)00302-4 [5] R. C. Srimal and B. N. Dhawan, “Pharmacology of Diferuloyl Methane (Curcumin), a Non-Steroidal Anti-Inflammatory Agent,” Journal of Pharmacy and Pharmacology, Vol. 25, No. 6, 1973, pp. 447-452. doi:10.1111/j.2042-7158.1973.tb09131.x [6] W. C. Jordan and C. R. Drew, “Curcumin––A Natural Herb with Anti-HIV Activity,” Journal of the National Medical Association, Vol. 88, No. 6, 1996, p. 333. [7] G. B. Mahady, S. L. Pendland, G. Yun and Z. Z. Lu, “Turmeric (Curcuma longa) and Curcumin Inhibit the Growth of Helicobacterpylori, a Group 1 Carcinogen,” Anticancer Research, Vol. 22, No. 6C, 2002, pp. 4179-4181. [8] M. K. Kim, G. J. Choi and H. S. Lee, “Fungicidal Property of Curcuma longa L. Rhizome-Derived Curcumin against Phytopathogenicfungi in a Greenhouse,” Journal of Agricultural and Food Chemistry, Vol. 51, No. 6, 2003, pp. 1578-1581. doi:10.1021/jf0210369 [9] R. C. Reddy, P. G. Vatsala, V. G. Keshamouni, G. Padmanaban and P. N. Rangarajan, “Curcumin for Malaria Therapy,” Biochemical and Biophysical Research Communications, Vol. 326, No. 2, 2005, pp. 472-474. doi:10.1016/j.bbrc.2004.11.051 [10] R. Kuttan, P. Bhanumathy, K. Nirmala and M. C. George, “Potentialanticancer Activity of Turmeric (Curcuma longa),” Cancer Letters, Vol. 29, No. 2, 1985, pp. 197-202. doi:10.1016/0304-3835(85)90159-4 [11] Y. Kiso, Y. Suzuki, N. Watanabe, Y. Oshima and H. Hikino, “Antihepatotoxic Principles of Curcuma longa Rhizomes,” Planta Medica, Vol. 49, No. 3, 1983, pp. 185-187. doi:10.1055/s-2007-969845 [12] N. Venkatesan, “Curcumin Attenuation of Acute Adriamycin Myocardialtoxicity in Rats,” British Journal of Pharmacology, Vol. 124, No. 3, 1998, pp. 425-427. doi:10.1038/sj.bjp.0701877 [13] N. Venkatesan, D. Punithavathi and V. Arumugam, “Curcuminprevents Adriamycin Nephrotoxicity in Rats,” British Journal of Pharmacology, Vol. 129, No. 2, 2000, pp. 231-234. doi:10.1038/sj.bjp.0703067 [14] R. Srivastava, M. Dikshit, R. C. Srimal and B. N. Dhawan, “Antithromboticeffect of Curcumin,” Thrombosis Research, Vol. 40, No. 3, 1985, pp. 413-417. doi:10.1016/0049-3848(85)90276-2 [15] M. Dikshit, L. Rastogi, R. Shukla and R. C. Srimal, “Prevention of Ischaemia-Induced Biochemical Changes by Curcumin & Quinidinein the Cat Heart,” Indian Journal of Medical Research, Vol. 101, 1995, pp. 31-35. [16] C. Nirmala and R. Puvanakrishnan, “Protective Role of Curcuminagainst Isoproterenol Induced Myocardial Infarction in Rats,” Molecular and Cellular Biochemistry, Vol. 159, No. 2, 1996, pp. 85-93. doi:10.1007/BF00420910 [17] C. Nirmala and R. Puvanakrishnan, “Effect of Curcumin on Certainlysosomal Hydrolases in Isoproterenol-Induced Myocardial Infarctionin Rats,” Biochemical Pharmacol-ogy, Vol. 51, No. 1, 1996, pp. 47-51. doi:10.1016/0006-2952(95)02118-3 [18] M. Srinivasan, “Effect of Curcumin on Blood Sugar as Seen in Adiabetic Subject,” Indian Journal of Medical Science, Vol. 26, No. 4, 1972, pp. 269-270. [19] P. S. Babu and K. Srinivasan, “Influence of Dietary Curcumin Andcholesterol on the Progression of Experimentally Induced Diabetesin Albino Rat,” Molecular and Cellular Biochemistry, Vol. 152, No. 1, 1995, pp. 13-21. [20] P. S. Babu and K. Srinivasan, “Hypolipidemic Action of Curcumin, the Active Principle of Turmeric (Curcuma longa) in Streptozotocin Induced Diabetic Rats,” Molecular and Cellular Biochemistry, Vol. 166, No. 1-2, 1997, pp. 169-175. doi:10.1023/A:1006819605211 [21] N. Arun and N. Nalini, “Efficacy of Turmeric on Blood Sugar and Polyolpathway in Diabetic Albino Rats,” Plant Foods for Human Nutrition, Vol. 57, No. 1, 2002, pp. 41-52. doi:10.1023/A:1013106527829 [22] S. D. Deodhar, R. Sethi and R. C. Srimal, “Preliminary Study Onantirheumatic Activity of Curcumin (Diferuloyl Methane),” Indian Journal of Medical Research, Vol. 71, 1980, pp. 632-634. [23] T. N. Shankar, N. V. Shantha, H. P. Ramesh, I. A. Murthy and V. S. Murthy, “Toxicity Studies on Turmeric (Curcuma longa): Acutetoxicity Studies in Rats, Guineapigs & Monkeys,” Indian Journal of Experimental Biology, Vol. 18, No. 1, 1980, pp. 73-75. [24] S. Qureshi, A. H. Shah and A. M. Ageel, “Toxicity Studies on Alpiniagalanga and Curcuma longa,” Planta Medica, Vol. 58, No. 2, 1992, pp. 124-127. doi:10.1055/s-2006-961412 [25] C. D. Lao, M. F. Demierre and V. K. Sondak, “Targeting Events Inmelanoma Carcinogenesis for the Prevention of Melanoma,” Expert Review of Anticancer Therapy, Vol. 6, No. 11, 2006, pp. 1559-1568. doi:10.1586/14737140.6.11.1559 [26] C. D. Lao, M. T. Ruffin, D. Normolle, D. D. Heath, S. I. Murray, J. M. Bailey, M. E. Boggs, J. Crowell, C. L. Rock and D. E. Brenner, “Dose Escalation of a Curcuminoid Formulation,” BMC Complementary and Alternative Medicine, Vol. 6, 2006, p. 10. doi:10.1186/1472-6882-6-10 [27] A. L. Cheng, C. H. Hsu, J. K. Lin, M. M. Hsu, Y. F. Ho, T. S. Shen, J. Y. Ko, J. T. Lin, B. R. Lin, W. Ming-Shiang, H. S. Yu, S. H. Jee, G. S. Chen, T. M. Chen, C. A. Chen, M. K. Lai, Y. S. Pu, M. H. Pan, Y. J. Wang, C. C. Tsai and C. Y. Hsieh, “Phase I Clinical Trial of Curcumin, a Chemopreventive Agent, in Patients with High-Risk or Pre-Malignant Lesions,” Anticancer Research, Vol. 21, No. 4B, 2001, pp. 2895-900. [28] G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran and P. S. Srinivas, “Influence of Piperine on the Pharmacokinetics of Curcuminin Animals and Human Volunteers,” Planta Medica, Vol. 64, No. 4, 1998, pp. 353-356. doi:10.1055/s-2006-957450 [29] B. B. Aggarwal, C. Sundaram, N. Malani and H. Ichikawa, “Curcumin: The Indian Solid Gold,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 1-75. doi:10.1007/978-0-387-46401-5_1 [30] C. H. Hsu and A. L. Cheng, “Clinical Studies with Curcumin,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 471-480. doi:10.1007/978-0-387-46401-5_21 [31] R. Ravichandran, “Preparation and Characterisation of Curcumin Nanosuspension for Enhanced Solubility and Dissolution Velocity,” International Journal of Nano and Biomaterials, Vol. 3, No. 2, 2010, pp. 153-186. doi:10.1504/IJNBM.2010.037803 [32] A. B. Mohsen, A. A. Abdulaziz, A. A. Mohamed and M. A. Mohamed, “In Vivo Evaluation of Arteether Liposomes,” International Journal of Pharmaceutics, Vol. 175, No. 1, 1998, pp. 1-7. doi:10.1016/S0378-5173(98)00182-3 [33] K. Maiti, K. Mukherjee, A. Gantait, B. P. Saha and P. K. Mukherjee, “Curcumin-Phospholipid Complex: Preparation, Therapeutic Evaluation and Pharmacokinetic Study in Rats,” International Journal of Pharmaceutics, Vol. 330, No. 1-2, 2007, pp. 155-163. doi:10.1016/j.ijpharm.2006.09.025 [34] N. Hussain, V. Jaitley and A. T. Florence, “Recent Advances in the Understanding of Uptake of Microparticulates across the Gastrointestinal Lymphatics,” Advanced Drug Delivery Reviews, Vol. 50, No. 1-2, 2001, pp. 107-142. doi:10.1016/S0169-409X(01)00152-1 [35] D. D. Stuart and T. M. Allen, “A New Liposomal Formulation for Antisenseoligodeoxynucleotides with Small Size, High Incorporation Efficiency and Good Stability,” Biochimica et Biophysica Acta, Vol. 146, 2000, pp. 3219-3229. [36] H. Yuan, J. Chen, Y. Z. Du, F. Q. Hu, S. Zeng and H. L. Zhao, “Studies on Oral Absorption of Stearic Acid SLN by a Novel Fluorometric Method,” Colloids and Surfaces B: Biointerfaces, Vol. 58, No. 2, 2007, pp. 157-164. doi:10.1016/j.colsurfb.2007.03.002 [37] R. N. Gursoy and S. Benita, “Self-Emulsifying Drug Delivery Systems (SEDDS) for Improved Oral Delivery of Lipophilic Drugs,” Biomedicine & Pharmacotherapy, Vol. 58, No. 3, 2004, pp. 173-182. doi:10.1016/j.biopha.2004.02.001 [38] S. J. Lim, M. K. Lee and C. K. Kim, “Altered Chemical and Biological Activities of All-Trans Retinoic Acid Incorporated in Solid Lipid Nanoparticle Powders,” Journal of Controlled Release, Vol. 100, No. 1, 2004, pp. 53-61. doi:10.1016/j.jconrel.2004.07.032 [39] T. Wisanu, L. Boonsom and L. Saisunee, “Flow Injection Analysis of Total Curcuminoids in Turmeric and Total Antioxidant Capacity Using 2,2Β0-Diphenyl-1-picrylhydrazyl Assay,” Food Chemistry, Vol. 112, 2009, pp. 494-499. [40] S. Schmidt, D. Gonzalez and H. Derendorf, “Significance of Protein Binding in Pharmacokinetics and Pharmacodynamics,” Journal of Pharmaceutical Sciences, Vol. 99, No. 3, 2010, pp. 1107-1122. doi:10.1002/jps.21916 [41] S. M. Moghimi, A. C. Hunter and J. C. Murray, “Long-Circulating and Target-Specific Nanoparticles: Theory to Practice,” Pharmacological Reviews, Vol. 53, No. 2, 2001, pp. 283-318. [42] E. Mastrobattista, G. A. Koning and G. Storm, “Immunoliposomes for the Targeted Delivery of Antitumor Drugs,” Advanced Drug Delivery Reviews, Vol. 40, No. 1-2, 1999, pp. 103-127. doi:10.1016/S0169-409X(99)00043-5 [43] K. Sou, S. Inenaga, S. Takeoka and E. Tsuchida, “Loading of Curcumin into Macrophages Using Lipid-Based Nanoparticles,” International Journal of Pharmaceutics, Vol. 352, No. 1-2, 2008, pp. 287-293. doi:10.1016/j.ijpharm.2007.10.033 [44] L. Li, B. Ahmed, K. Mehta and R. Kurzrock, “Liposomal Curcumin with and without Oxaliplatin: Effects on Cell Growth, Apoptosis, and Angiogenesis in Colorectal Cancer,” Molecular Cancer Therapeutics, Vol. 6, 2007, 1276-1282. doi:10.1158/1535-7163.MCT-06-0556 [45] Z. Ma, A. Shayeganpour, D. R. Brocks, A. Lavasanifar and J. Samuel, “Highperformance Liquid Chromatography Analysis of Curcumin in Rat Plasma: Application to Pharmacokinetics of Polymeric Micellar Formulation of Curcumin,” Biomedical Chromatography, Vol. 21, No. 5, 2007, pp. 546-552. doi:10.1002/bmc.795 [46] C. A. Mosley, D. C. Liotta and J. P. Snyder, “Highly Active Anticancer Curcumin Analogues,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 77-103. doi:10.1007/978-0-387-46401-5_2 [47] A. Preetha, R. Banerjee and N. Huilgol, “Tensiometric Profiles and Their Modulation by Cholesterol: Implications in Cervical Cancer,” Cancer Investigation, Vol. 25, No. 3, 2007, pp. 172-181. doi:10.1080/07357900701209053 [48] H. Ohori, H. Yamakoshi, M. Tomizawa, M. Shibuya, Y. Kakudo, A. Takahashi, S. Takahashi, S. Kato, T. Suzuki, C. Ishioka, Y. Iwabuchi and H. Shibata, “Synthesis and Biological Analysis of New Curcumin Analogues Bearing an Enhanced Potential for the Medicinal Treatment of Cancer,” Molecular Cancer Therapeutics, Vol. 5, 2006, pp. 2563-2571. doi:10.1158/1535-7163.MCT-06-0174 [49] C. Karikar, A. Maitra, S. Bisht, G. Feldmann, S. Soni and R. Ravi, “Polymeric Nanoparticle-Encapsulated Curcumin (‘Nanoparticulate Curcumin’): A Novel Strategy for Human Cancer Therapy,” Journal of Nanobiotechnology, Vol. 5, 2007, p. 3. doi:10.1186/1477-3155-5-3 [50] W. Tiyaboonchai, W. Tungpradit and P. Plianbangchang, “Formulationand Characterization of Curcuminoids Loaded Solid Lipid Nanoparticles,” International Journal of Pharmaceutics, Vol. 337, No. 1-2, 2007, pp. 299-306. doi:10.1016/j.ijpharm.2006.12.043 [51] U. K. Parashar, P. S. Saxena and A. Srivastava, “Role of Na-nomaterials in Biotechnology,” Digest Journal of Nanomaterials and Biostructures, Vol. 3, No. 2, 2008, pp. 81-87. [52] R. Ravichandran, “Nanoparticles in Drug Delivery: Potential Green Nanobiomedicine Applications,” International Journal of Green Nanotechnology: Biomedicine, Vol. 1, No. 2, 2009, pp. B108-B130. [53] R. Ravichandran, “Nanotechnology-Based Drug Delivery Systems,” NanoBiotechnology, Vol. 5, No. 1, 2010, pp. 17-33. doi:10.1007/s12030-009-9028-2 [54] M. Sun, X. Su, B. Ding, X. L. He, X. J. Liu, A. H. Yu, H. X. Lou and G. X. Zhai, “Advances in Nanotechnology-Based Delivery Systems for Curcumin,” Nanomedicine, Vol. 7, No. 7, 2012, pp. 1085-1100. doi:10.2217/nnm.12.80
[1] B. B. Aggarwal, A. Kumar and A. C. Bharti, “Anticancer Potential of Curcumin: Preclinical and Clinical Studies,” Anticancer Research, Vol. 23, No. 1A, 2003, pp. 363-398. [2] O. P. Sharma, “Antioxidant Activity of Curcumin and Related Compounds,” Biochemical Pharmacology, Vol. 25, No. 15, 1976, pp. 1811-1812. doi:10.1016/0006-2952(76)90421-4 [3] A. J. Ruby, G. Kuttan, K. D. Babu, K. N. Rajasekharan and R. Kuttan, “Anti-Tumour and Antioxidant Activity of Natural Curcuminoids,” Cancer Letters, Vol. 94, No. 1, 1995, pp. 79-83. doi:10.1016/0304-3835(95)03827-J [4] Y. Sugiyama, S. Kawakishi and T. Osawa, “Involvement of the Diketone Moiety in the Antioxidative Mechanism of Tetrahydrocurcumin,” Biochemical Pharmacology, Vol. 52, No. 4, 1996, pp. 519-525. doi:10.1016/0006-2952(96)00302-4 [5] R. C. Srimal and B. N. Dhawan, “Pharmacology of Diferuloyl Methane (Curcumin), a Non-Steroidal Anti-Inflammatory Agent,” Journal of Pharmacy and Pharmacology, Vol. 25, No. 6, 1973, pp. 447-452. doi:10.1111/j.2042-7158.1973.tb09131.x [6] W. C. Jordan and C. R. Drew, “Curcumin––A Natural Herb with Anti-HIV Activity,” Journal of the National Medical Association, Vol. 88, No. 6, 1996, p. 333. [7] G. B. Mahady, S. L. Pendland, G. Yun and Z. Z. Lu, “Turmeric (Curcuma longa) and Curcumin Inhibit the Growth of Helicobacterpylori, a Group 1 Carcinogen,” Anticancer Research, Vol. 22, No. 6C, 2002, pp. 4179-4181. [8] M. K. Kim, G. J. Choi and H. S. Lee, “Fungicidal Property of Curcuma longa L. Rhizome-Derived Curcumin against Phytopathogenicfungi in a Greenhouse,” Journal of Agricultural and Food Chemistry, Vol. 51, No. 6, 2003, pp. 1578-1581. doi:10.1021/jf0210369 [9] R. C. Reddy, P. G. Vatsala, V. G. Keshamouni, G. Padmanaban and P. N. Rangarajan, “Curcumin for Malaria Therapy,” Biochemical and Biophysical Research Communications, Vol. 326, No. 2, 2005, pp. 472-474. doi:10.1016/j.bbrc.2004.11.051 [10] R. Kuttan, P. Bhanumathy, K. Nirmala and M. C. George, “Potentialanticancer Activity of Turmeric (Curcuma longa),” Cancer Letters, Vol. 29, No. 2, 1985, pp. 197-202. doi:10.1016/0304-3835(85)90159-4 [11] Y. Kiso, Y. Suzuki, N. Watanabe, Y. Oshima and H. Hikino, “Antihepatotoxic Principles of Curcuma longa Rhizomes,” Planta Medica, Vol. 49, No. 3, 1983, pp. 185-187. doi:10.1055/s-2007-969845 [12] N. Venkatesan, “Curcumin Attenuation of Acute Adriamycin Myocardialtoxicity in Rats,” British Journal of Pharmacology, Vol. 124, No. 3, 1998, pp. 425-427. doi:10.1038/sj.bjp.0701877 [13] N. Venkatesan, D. Punithavathi and V. Arumugam, “Curcuminprevents Adriamycin Nephrotoxicity in Rats,” British Journal of Pharmacology, Vol. 129, No. 2, 2000, pp. 231-234. doi:10.1038/sj.bjp.0703067 [14] R. Srivastava, M. Dikshit, R. C. Srimal and B. N. Dhawan, “Antithromboticeffect of Curcumin,” Thrombosis Research, Vol. 40, No. 3, 1985, pp. 413-417. doi:10.1016/0049-3848(85)90276-2 [15] M. Dikshit, L. Rastogi, R. Shukla and R. C. Srimal, “Prevention of Ischaemia-Induced Biochemical Changes by Curcumin & Quinidinein the Cat Heart,” Indian Journal of Medical Research, Vol. 101, 1995, pp. 31-35. [16] C. Nirmala and R. Puvanakrishnan, “Protective Role of Curcuminagainst Isoproterenol Induced Myocardial Infarction in Rats,” Molecular and Cellular Biochemistry, Vol. 159, No. 2, 1996, pp. 85-93. doi:10.1007/BF00420910 [17] C. Nirmala and R. Puvanakrishnan, “Effect of Curcumin on Certainlysosomal Hydrolases in Isoproterenol-Induced Myocardial Infarctionin Rats,” Biochemical Pharmacol-ogy, Vol. 51, No. 1, 1996, pp. 47-51. doi:10.1016/0006-2952(95)02118-3 [18] M. Srinivasan, “Effect of Curcumin on Blood Sugar as Seen in Adiabetic Subject,” Indian Journal of Medical Science, Vol. 26, No. 4, 1972, pp. 269-270. [19] P. S. Babu and K. Srinivasan, “Influence of Dietary Curcumin Andcholesterol on the Progression of Experimentally Induced Diabetesin Albino Rat,” Molecular and Cellular Biochemistry, Vol. 152, No. 1, 1995, pp. 13-21. [20] P. S. Babu and K. Srinivasan, “Hypolipidemic Action of Curcumin, the Active Principle of Turmeric (Curcuma longa) in Streptozotocin Induced Diabetic Rats,” Molecular and Cellular Biochemistry, Vol. 166, No. 1-2, 1997, pp. 169-175. doi:10.1023/A:1006819605211 [21] N. Arun and N. Nalini, “Efficacy of Turmeric on Blood Sugar and Polyolpathway in Diabetic Albino Rats,” Plant Foods for Human Nutrition, Vol. 57, No. 1, 2002, pp. 41-52. doi:10.1023/A:1013106527829 [22] S. D. Deodhar, R. Sethi and R. C. Srimal, “Preliminary Study Onantirheumatic Activity of Curcumin (Diferuloyl Methane),” Indian Journal of Medical Research, Vol. 71, 1980, pp. 632-634. [23] T. N. Shankar, N. V. Shantha, H. P. Ramesh, I. A. Murthy and V. S. Murthy, “Toxicity Studies on Turmeric (Curcuma longa): Acutetoxicity Studies in Rats, Guineapigs & Monkeys,” Indian Journal of Experimental Biology, Vol. 18, No. 1, 1980, pp. 73-75. [24] S. Qureshi, A. H. Shah and A. M. Ageel, “Toxicity Studies on Alpiniagalanga and Curcuma longa,” Planta Medica, Vol. 58, No. 2, 1992, pp. 124-127. doi:10.1055/s-2006-961412 [25] C. D. Lao, M. F. Demierre and V. K. Sondak, “Targeting Events Inmelanoma Carcinogenesis for the Prevention of Melanoma,” Expert Review of Anticancer Therapy, Vol. 6, No. 11, 2006, pp. 1559-1568. doi:10.1586/14737140.6.11.1559 [26] C. D. Lao, M. T. Ruffin, D. Normolle, D. D. Heath, S. I. Murray, J. M. Bailey, M. E. Boggs, J. Crowell, C. L. Rock and D. E. Brenner, “Dose Escalation of a Curcuminoid Formulation,” BMC Complementary and Alternative Medicine, Vol. 6, 2006, p. 10. doi:10.1186/1472-6882-6-10 [27] A. L. Cheng, C. H. Hsu, J. K. Lin, M. M. Hsu, Y. F. Ho, T. S. Shen, J. Y. Ko, J. T. Lin, B. R. Lin, W. Ming-Shiang, H. S. Yu, S. H. Jee, G. S. Chen, T. M. Chen, C. A. Chen, M. K. Lai, Y. S. Pu, M. H. Pan, Y. J. Wang, C. C. Tsai and C. Y. Hsieh, “Phase I Clinical Trial of Curcumin, a Chemopreventive Agent, in Patients with High-Risk or Pre-Malignant Lesions,” Anticancer Research, Vol. 21, No. 4B, 2001, pp. 2895-900. [28] G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran and P. S. Srinivas, “Influence of Piperine on the Pharmacokinetics of Curcuminin Animals and Human Volunteers,” Planta Medica, Vol. 64, No. 4, 1998, pp. 353-356. doi:10.1055/s-2006-957450 [29] B. B. Aggarwal, C. Sundaram, N. Malani and H. Ichikawa, “Curcumin: The Indian Solid Gold,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 1-75. doi:10.1007/978-0-387-46401-5_1 [30] C. H. Hsu and A. L. Cheng, “Clinical Studies with Curcumin,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 471-480. doi:10.1007/978-0-387-46401-5_21 [31] R. Ravichandran, “Preparation and Characterisation of Curcumin Nanosuspension for Enhanced Solubility and Dissolution Velocity,” International Journal of Nano and Biomaterials, Vol. 3, No. 2, 2010, pp. 153-186. doi:10.1504/IJNBM.2010.037803 [32] A. B. Mohsen, A. A. Abdulaziz, A. A. Mohamed and M. A. Mohamed, “In Vivo Evaluation of Arteether Liposomes,” International Journal of Pharmaceutics, Vol. 175, No. 1, 1998, pp. 1-7. doi:10.1016/S0378-5173(98)00182-3 [33] K. Maiti, K. Mukherjee, A. Gantait, B. P. Saha and P. K. Mukherjee, “Curcumin-Phospholipid Complex: Preparation, Therapeutic Evaluation and Pharmacokinetic Study in Rats,” International Journal of Pharmaceutics, Vol. 330, No. 1-2, 2007, pp. 155-163. doi:10.1016/j.ijpharm.2006.09.025 [34] N. Hussain, V. Jaitley and A. T. Florence, “Recent Advances in the Understanding of Uptake of Microparticulates across the Gastrointestinal Lymphatics,” Advanced Drug Delivery Reviews, Vol. 50, No. 1-2, 2001, pp. 107-142. doi:10.1016/S0169-409X(01)00152-1 [35] D. D. Stuart and T. M. Allen, “A New Liposomal Formulation for Antisenseoligodeoxynucleotides with Small Size, High Incorporation Efficiency and Good Stability,” Biochimica et Biophysica Acta, Vol. 146, 2000, pp. 3219-3229. [36] H. Yuan, J. Chen, Y. Z. Du, F. Q. Hu, S. Zeng and H. L. Zhao, “Studies on Oral Absorption of Stearic Acid SLN by a Novel Fluorometric Method,” Colloids and Surfaces B: Biointerfaces, Vol. 58, No. 2, 2007, pp. 157-164. doi:10.1016/j.colsurfb.2007.03.002 [37] R. N. Gursoy and S. Benita, “Self-Emulsifying Drug Delivery Systems (SEDDS) for Improved Oral Delivery of Lipophilic Drugs,” Biomedicine & Pharmacotherapy, Vol. 58, No. 3, 2004, pp. 173-182. doi:10.1016/j.biopha.2004.02.001 [38] S. J. Lim, M. K. Lee and C. K. Kim, “Altered Chemical and Biological Activities of All-Trans Retinoic Acid Incorporated in Solid Lipid Nanoparticle Powders,” Journal of Controlled Release, Vol. 100, No. 1, 2004, pp. 53-61. doi:10.1016/j.jconrel.2004.07.032 [39] T. Wisanu, L. Boonsom and L. Saisunee, “Flow Injection Analysis of Total Curcuminoids in Turmeric and Total Antioxidant Capacity Using 2,2Β0-Diphenyl-1-picrylhydrazyl Assay,” Food Chemistry, Vol. 112, 2009, pp. 494-499. [40] S. Schmidt, D. Gonzalez and H. Derendorf, “Significance of Protein Binding in Pharmacokinetics and Pharmacodynamics,” Journal of Pharmaceutical Sciences, Vol. 99, No. 3, 2010, pp. 1107-1122. doi:10.1002/jps.21916 [41] S. M. Moghimi, A. C. Hunter and J. C. Murray, “Long-Circulating and Target-Specific Nanoparticles: Theory to Practice,” Pharmacological Reviews, Vol. 53, No. 2, 2001, pp. 283-318. [42] E. Mastrobattista, G. A. Koning and G. Storm, “Immunoliposomes for the Targeted Delivery of Antitumor Drugs,” Advanced Drug Delivery Reviews, Vol. 40, No. 1-2, 1999, pp. 103-127. doi:10.1016/S0169-409X(99)00043-5 [43] K. Sou, S. Inenaga, S. Takeoka and E. Tsuchida, “Loading of Curcumin into Macrophages Using Lipid-Based Nanoparticles,” International Journal of Pharmaceutics, Vol. 352, No. 1-2, 2008, pp. 287-293. doi:10.1016/j.ijpharm.2007.10.033 [44] L. Li, B. Ahmed, K. Mehta and R. Kurzrock, “Liposomal Curcumin with and without Oxaliplatin: Effects on Cell Growth, Apoptosis, and Angiogenesis in Colorectal Cancer,” Molecular Cancer Therapeutics, Vol. 6, 2007, 1276-1282. doi:10.1158/1535-7163.MCT-06-0556 [45] Z. Ma, A. Shayeganpour, D. R. Brocks, A. Lavasanifar and J. Samuel, “Highperformance Liquid Chromatography Analysis of Curcumin in Rat Plasma: Application to Pharmacokinetics of Polymeric Micellar Formulation of Curcumin,” Biomedical Chromatography, Vol. 21, No. 5, 2007, pp. 546-552. doi:10.1002/bmc.795 [46] C. A. Mosley, D. C. Liotta and J. P. Snyder, “Highly Active Anticancer Curcumin Analogues,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 77-103. doi:10.1007/978-0-387-46401-5_2 [47] A. Preetha, R. Banerjee and N. Huilgol, “Tensiometric Profiles and Their Modulation by Cholesterol: Implications in Cervical Cancer,” Cancer Investigation, Vol. 25, No. 3, 2007, pp. 172-181. doi:10.1080/07357900701209053 [48] H. Ohori, H. Yamakoshi, M. Tomizawa, M. Shibuya, Y. Kakudo, A. Takahashi, S. Takahashi, S. Kato, T. Suzuki, C. Ishioka, Y. Iwabuchi and H. Shibata, “Synthesis and Biological Analysis of New Curcumin Analogues Bearing an Enhanced Potential for the Medicinal Treatment of Cancer,” Molecular Cancer Therapeutics, Vol. 5, 2006, pp. 2563-2571. doi:10.1158/1535-7163.MCT-06-0174 [49] C. Karikar, A. Maitra, S. Bisht, G. Feldmann, S. Soni and R. Ravi, “Polymeric Nanoparticle-Encapsulated Curcumin (‘Nanoparticulate Curcumin’): A Novel Strategy for Human Cancer Therapy,” Journal of Nanobiotechnology, Vol. 5, 2007, p. 3. doi:10.1186/1477-3155-5-3 [50] W. Tiyaboonchai, W. Tungpradit and P. Plianbangchang, “Formulationand Characterization of Curcuminoids Loaded Solid Lipid Nanoparticles,” International Journal of Pharmaceutics, Vol. 337, No. 1-2, 2007, pp. 299-306. doi:10.1016/j.ijpharm.2006.12.043 [51] U. K. Parashar, P. S. Saxena and A. Srivastava, “Role of Na-nomaterials in Biotechnology,” Digest Journal of Nanomaterials and Biostructures, Vol. 3, No. 2, 2008, pp. 81-87. [52] R. Ravichandran, “Nanoparticles in Drug Delivery: Potential Green Nanobiomedicine Applications,” International Journal of Green Nanotechnology: Biomedicine, Vol. 1, No. 2, 2009, pp. B108-B130. [53] R. Ravichandran, “Nanotechnology-Based Drug Delivery Systems,” NanoBiotechnology, Vol. 5, No. 1, 2010, pp. 17-33. doi:10.1007/s12030-009-9028-2 [54] M. Sun, X. Su, B. Ding, X. L. He, X. J. Liu, A. H. Yu, H. X. Lou and G. X. Zhai, “Advances in Nanotechnology-Based Delivery Systems for Curcumin,” Nanomedicine, Vol. 7, No. 7, 2012, pp. 1085-1100. doi:10.2217/nnm.12.80