BioaVailability of Curcumin: Problems and Promises
free curcumin, nanocurcumin also inhibits activation of the transcription factor NFκB, and reduces steady state levels of pro-inflammatory cytokines like interleukins and TNF-R. However, the authors neither determined the in ViVo effect of nanocurcumin in mice nor its biodistribution to show any potential increase in efficacy of nanaocurcumin over free curcumin in vivo.61 Solid lipid nanoparticles (SLNs) loaded with curcuminoids for topical application were developed and characterized by Tiyaboonchai et al. Curcuminoid loaded SLNs having 450 nm size were found to be stable for 6 months at room temperature and gave prolonged in Vitro release of curcuminoids up to 12 h. Furthermore, the light and oxygen sensitivity of curcuminoids was strongly reduced by incorporating curcuminoids into this unique type of formulation. An in ViVo study with healthy volunteers reveled the improved efficiency of a topical application cream containing curcuminoid loaded SLNs over that containing free curcuminoids.62 Overall, nanoparticle based systems for curcumin delivery is still in its infancy and much progress
is warranted in this area.
Complexes. Liposomes are excellent drug delivery systems since they can carry both hydrophilic and hydrophobic molecules. Li et al. investigated the in Vitro and in ViVo antitumor activity of liposomal curcumin against human pancreatic carcinoma cells and demonstrated that liposomal curcumin inhibits pancreatic carcinoma growth and, in addition, exhibits antiangiogenic effects. Liposomal curcumin suppressed the pancreatic carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. In the in ViVo part of this study, the effect of liposomal curcumin was evaluated in comparison to untreated and liposomal vehicle treated mice. Comparison of effect of liposmal curcumin with free curcumin and biodistribution profiles of liposomal curcumin over free curcumin have yet to be evaluated to confirm the enhancement of curcumin bioavail- ability by liposomal curcumin.63 The preclinical anticancer activity of a liposomal curcumin formulation in colorectal cancer was also recently evaluated. This study also compared the efficacy of liposomal curcumin with that of oxaliplatin, a standard chemotherapeutic agent for colorectal cancer. There was synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin in Colo205 cells. Thus, this study established the comparable or greater
Karikar, C.; Maitra, A.; Bisht, S.; Feldmann, G.; Soni, S.; Ravi,
Polymeric nanoparticle-encapsulated curcumin (“nanocur- cumin”): a novel strategy for human cancer therapy. J. Nanobio- technol. 2007, 5, 3.
Tiyaboonchai, W.; Tungpradit, W.; Plianbangchang, P. .Formula- tion and characterization of curcuminoids loaded solid lipid nanoparticles. Int. J. Pharm. 2007, 337 (1–2), 299–306.
Li, L.; Braiteh, F. S.; Kurzrock, R. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 2005, 104 (6), 1322–31.
growth-inhibitory and apoptotic effects of liposomal cur- cumin with oxaliplatin both in vitro and in vivo in colorectal cancer. This group is currently developing liposomal cur- cumin for introduction into the clinical setting.64 Ruby et al. also reported the antitumor and antioxidant activities of neutral unilamellar liposomal curcuminoids in mice.3 Nev- ertheless, in ViVo preclinical studies are warranted to show the increased bioavailability of liposomal curcumin over free curcumin. Kanwar et al. evaluated the in Vitro cellular uptake of liposomal and albumin loaded curcumin. From these studies it was found that liposomal vehicle is capable of loading more curcumin in to cells than either HSA or aqueous-DMSO, and lymphoma cells showed preferential uptake of curcumin to lymphocytes.65
Micelles and phospholipid complexes can improve the gastrointestinal absorption of natural drugs, thereby giving higher plasma levels and lower kinetic elimination resulting in improved bioavailability. The intestinal absorption of curcumin and micellar curcumin formulation with phospho- lipid and bile salt was evaluated using an in Vitro model consisting of everted rat intestinal sacs. This study suggested biological transformation of curcumin during absorption. Further, the in Vitro intestinal absorption of curcumin was found to increase from 47% to 56% when the same was present in micelles.66 Pharmacokinetic studies by Ma et al. also demonstrated that a polymeric micellar curcumin gave a 60-fold higher biological half-life for curcumin in rats compared to curcumin solubilized in a mixture of DMA, PEG and dextrose.67 Phospholipid complex formulations of several natural drugs, such as silymarin68 and dolichol,69 have been found to show improved bioavailability. Liu et al., for example, showed a significant improvement in curcumin bioavailability due to curcumin-phospholipid complex for- mation. In this study, curcumin (100 mg/kg) and cur- cumin–phospholipid complex (corresponding to 100 mg/kg of curcumin) were administered orally to Sprague–Dawley male rats. Curcumin–phospholipid complex showed a maxi- mum plasma curcumin level of 600 ng/mL 2.33 h after oral administration as opposed to that of free curcumin having maximum plasma concentration of 267 ng/mL after 1.62 h of oral dosing. About a 1.5-fold increase in curcumin half- life in rats was found in this study for the curcumin phospholipid complex over free curcumin. These results indicate that the curcumin phospholipid complex can sig-
Li, L.; Ahmed, B.; Mehta, K.; Kurzrock, R. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol. Cancer Ther. 2007, 6 (4), 1276–82.
Kunwar, A.; Barik, A.; Pandey, R.; Priyadarsini, K. I. Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study. Biochim. Bio- phys. Acta 2006, 1760 (10), 1513–20.
Suresh, D; Srinivasan, K. Studies on the in vitro absorption of spice principles––Curcumin, capsaicin and piperine in rat intes- tines. Food Chem. Toxicol. 2007, 45 (8), 1437–42.
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