CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY
DOI:
https://doi.org/10.22159/ijpps.2016v8i12.15093Keywords:
Curcumin, Brain, CUR-CA-THIONE, Solubility, TissueAbstract
Objective: Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.
Methods: A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for in vitro release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.
Results: A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC50: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for in vitro release profile at different pH with average release obtained between 20-30 min. In vivo kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.
Conclusion: The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.
Downloads
References
Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phyther Res 2012;26:1719–25.
Chanpoo M, Petchpiboonthai H, Panyarachun B, Anupunpisit V. Effect of curcumin in the amelioration of pancreatic islets in streptozotocin-induced diabetic mice. J Med Assoc Thai 2010;93 Suppl 6:152-9.
Hong D, Zeng X, Xu W, Ma J, Tong Y, Chen Y. Altered profiles of gene expression in curcumin-treated rats with experimentally induced myocardial infarction. Pharmacol Res 2010;61:142–8.
Ranjan AP, Mukerjee A, Helson L, Gupta R, Vishwanatha JK. Efficacy of liposomal curcumin in a human pancreatic tumor xenograft model: inhibition of tumor growth and angiogenesis. Anticancer Res 2013;33:3603–9.
Quitschke W, Steinhauff N, Rooney J. The effect of cyclodextrin-solubilized curcuminoids on amyloid plaques in Alzheimer transgenic mice: brain uptake and metabolism after intravenous and subcutaneous injection. Alzheimers Res Ther 2013;5:16.
Holder G, Plummer J, Ryan A. The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica 1978;8:761–8.
Ravindranath V, Chandrasekhara N. In vitro studies on the intestinal absorption of curcumin in rats. Toxicology 1981;20:251–7.
Ringman J, Frautschy S, Cole G, Masterman D, Cummings J. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer’s Res 2005;2:131–6.
Anand P, Kunnumakkara A, Newman R, Aggarwal B. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807–18.
Shelat P, Mandowara V, Gupta D, Patel S. Formulation of curcuminoid loaded solid lipid nanoparticles in order to improve oral bioavailability. Int J Pharm Pharm Sci 2015;7:7–11.
Ng T, Chiam P, Lee T, Chua H, Lim L, Kua E. Curry consumption and cognitive function in the elderly. Am J Epidemiol 2006;164:898–906.
Begum A, Jones M, Lim G, Morihara T, Kim P, Heath D, et al. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther 2008;326:196–208.
Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT BB. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer, mouse model. J Neurochem 2007;102:1094–104.
Leung M, Kee T. Effective stabilization of curcumin by association to plasma proteins: human serum albumin and fibrinogen. Langmuir 2009;25:5773–7.
Wang Y, Pan M, Cheng A, Lin L, Ho Y, Hsieh C, et al. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 1997;15:1867–76.
Vyas N, Patel S. Simultaneous estimation of curcuminoids, piperine, and gallic acid in an ayurvedic formulation by the validated high-performance thin layer chromatography method. Asian J Pharm Clin Res 2016;9 Suppl 2:117-22.
Kurmi R, Mishra D, Jain D. Solid dispersion: a novel means of solubility enhancement. J Crit Rev 2016;3:1–8.
Sies H. Glutathione and its role in cellular functions. Free Radical Biol Med 1999;27:916–21.
N Willmott, GA Magee, J Cummings G. Doxorubicin-loaded casein microspheres: protean nature of drug incorporation. J Pharm Pharmacol 1992;44:472–5.
Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with the solid matrix for oral drug delivery. AAPS PharmSciTech 2011;12:62–76.
Suzuki K, Price J. Microencapsulation and dissolution properties of a neuroleptic in a biodegradable polymer, poly(d,l-lactide). J Pharm Sci 1985;74:21–4.
Athira GK, Jyothi AN. Preparation and characterization of curcumin loaded cassava starch nanoparticles with improved cellular absorption. Int J Pharm Pharm Sci 2014;6:171–6.
Bhalekar M, Pokharkar V, Madgulkar A, Patil N, Patil N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery. AAPS PharmSciTech 2009;10:289–96.
Muddukrishna B, Dengale S, Shenoy G, Bhat K. Preparation, solid state characterisation of paclitaxel and naringen cocrystals with improved solubility. Int J Appl Pharm 2016;8:32-7.
Wan S, Sun Y, Qi X, Tan F. Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech 2012;13:159–66.
Jangde R, Singh D. Investigation of drug-excipients compatibility of ellagic acid for development of formulation containing lipososmes. UK J Pharm Biosci 2014;2:15–8.
Blois M. Antioxidant determinations by the use of a stable free radical. Nature 1958;181:1199–200.
Kumar A, Singh M, Singh P, Singh S, Raj P, Kapil D. Antioxidant efficacy and curcumin content of turmeric (Curcuma longa L.). Int J Curr Pharm Res 2016;8:112-4.
Jain A, Dhawan V, Sarmento B, Nagarsenker M. In vitro and ex vivo evaluations of lipid anti-cancer nanoformulations: insights and assessment of bioavailability enhancement. AAPS PharmSciTech 2016;17:553-71.
Rachmawati H, Edityaningrum C, Mauludin R. Molecular inclusion complex of the curcumin-β-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel. AAPS PharmSciTech 2013;14:1303–12.
John F, George J. Curcumin encapsulated alginate/pluronic block copolymer micelles as a promising therapeutic agent. UK J Pharm Biosci 2014;2:6-12.
Berginc K, Skalko-Basnet N, Basnet P, Kristl A. Development and evaluation of an in vitro vaginal model for assessment of drug’s biopharmaceutical properties: curcumin. AAPS PharmSciTech 2012;13:1045–53.
Teixeira C, Mendonça L, Bergamaschi M, Queiroz R, Souza G, Antunes L, et al. Microparticles containing solid curcumin dispersion: stability, bioavailability, and anti-inflammatory activity. AAPS PharmSciTech 2015;17:252–61.
Kakkar V, Kaur I. Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem Toxicol 2011;49:2906–13.
Agrawal R, Sandhu S, Sharma I, Kaur I. Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation. AAPS PharmSciTech 2015;16:364–74.
Yadav V, Suresh S, Devi K, Yadav S. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. AAPS PharmSciTech 2009;10:752–62.
Zhongfa L, Chiu M, Wang J, Chen W, Yen W, Fan-Havard P, et al. Enhancement of curcumin oral absorption and pharmaco-kinetics of curcuminoids and curcumin metabolites in mice. Cancer Chemother Pharmacol 2012;69:679–89.
Yang K, Lin L, Tseng T, Wang S, Tsai T. Oral bioavailability of curcumin in rat and the herbal analysis from curcuma longa by LC–MS/MS. J Chromatogr B 2007;853:183–9.
Published
How to Cite
Issue
Section
