We report here the potential of Pluronic tri-block copolymer micelles for the formulation of curcumin, a natural dietary compound having great therapeutic potential against many diseases including cancer. Two most commonly used Pluronic F127 and F68 were used for the formulation and analyzed for curcumin encapsulation efficiency and stability. The encapsulation of drug in micelle was highly dependent on drug-to-copolymer ratio. Pluronic F127 showed better encapsulation efficiency than Pluronic F68. In vitro release profile demonstrated slower and sustained release of curcumin from Pluronic micelles. The lyophilized form of the formulations exhibited good stability for long-term storage. The physical interaction of curcumin with Pluronic was evident by XRD analysis, UV-visible, fluorescence, and FT-IR spectroscopy. AFM study showed that the drug-encapsulated micelles were spherical in shape with diameters below 100 nm. The in vitro cytotoxicity of the drug formulations was investigated with HeLa cancer cells. Pluronic-encapsulated curcumin showed comparable anticancer activity with free curcumin.
Howells, L.M. , Moiseeva, E.P., Neal, C.P. et al., Predicting the Physiological Relevance of In Vitro Cancer Preventive Activities of Phytochemicals, Acta Pharmacol. Sin., 2007: 28: 1274-1304.
2.
Maheshwari, R.K., Singh, A.K., Gaddipati, J. and Srimal, R.C.Multiple Biological Activities of Curcumin: A Short Review, Life Sci., 2006: 78: 2081-2087.
3.
Aggarwal, B.B. and Harikumar, K.B.Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases, Int. J. Biochem. Cell Biol., 2009: 41: 40-59.
4.
Goel, A., Kunnumakkara, A.B. and Aggarwal, B.B.Curcumin as ‘Curecumin’: From Kitchen to Clinic, Biochem. Pharmacol., 2008: 75: 787-809.
5.
Sharma, R.A. , Gescher, A.J. and Steward, W.P.Curcumin: The Story So Far, Eur. J. Cancer, 2005: 41: 1955-1968.
6.
Anand, P., Kunnumakkara, A.B., Newman, R.A. and Aggarwal, B.B.Bioavailability of Curcumin: Problems and Promises, Mol. Pharm. , 2007: 4: 807-818.
7.
Bisht, S., Feldmann, G., Soni, S. et al., Polymeric Nanoparticle-encapsulated Curcumin (Nanocurcumin): A Novel Strategy for Human Cancer Therapy, J. Nanobiotechnology. , 2007: 5: 3.
8.
Sahu, A., Kasoju, N. and Bora, U.Fluorescence Study of the Curcumin- casein Micelle Complexation and Its Application as a Drug Nanocarrier to Cancer Cells, Biomacromolecules, 2008: 9: 2905-2912.
9.
Sou, K., Inenaga, S., Takeoka, S. and Tsuchida, E.Loading of Curcumin into Macrophages Using Lipid-based Nanoparticles, Int. J. Pharm., 2008: 352: 287-293.
10.
Ma, Z., Haddadi, A., Molavi, O., et al. Micelles of Poly(Ethylene Oxide)-b-Poly(ε-Caprolactone) as Vehicles for the Solubilization, Stabilization, and Controlled Delivery of Curcumin, J. Biomed. Mater. Res. A, 2008 : 86: 300-310.
11.
Sahu, A., Bora, U., Kasoju, N. and Goswami, P.Synthesis of Novel Biodegradable and Self-assembling Methoxy Poly (Ethylene Glycol) Palmitate Nanocarrier for Curcumin Delivery to Cancer Cells, Acta Biomater., 2008: 4: 1752-1761.
12.
Kwon, G.S. and Kataoka, K.Block Copolymer Micelles as Long-circulating Drug Vehicles, Adv. Drug Deliv. Rev., 1995: 16: 295-309.
13.
Allen, C., Maysinger, D. and Eisenberg, A.Nano-engineering Block Copolymer Aggregates for Drug Delivery, Colloids Surf. B Biointerfaces, 1999: 16: 3-27.
14.
Bromberg, L.Polymeric Micelles in Oral Chemotherapy, J. Contr. Release , 2008: 128: 99-112.
15.
Batrakova, E.V. and Kabanov, A.V.Pluronic Block Copolymers: Evolution of Drug Delivery Concept from Inert Nanocarriers to Biological Response Modifiers , J. Contr. Release, 2008: 130: 98-106.
16.
Chowdhary, R.K. , Chansarkar, N., Sharif, I., Hioka, N. and Dolphin, D.Formulation of Benzoporphyrin Derivatives in Pluronics, Photochem Photobiol., 2003: 77: 299-303.
17.
Kabanov, A.V. , Batrakova, E.V. and Alakhov, V.Y.Pluronic® Block Copolymers as Novel Polymer Therapeutics for Drug and Gene Delivery, J. Contr. Release, 2002: 82: 189-212.
18.
Chiappetta, D.A. and Sosnik, A.Poly(Ethylene Oxide)-Poly(Propylene Oxide) Block Copolymer Micelles as Drug Delivery Agents: Improved Hydrosolubility, Stability and Bioavailability of Drugs, Eur. J. Pharm. Biopharm. , 2007: 66: 303-317.
19.
Croy, S.C. and Kwon, G.S.The Effects of Pluronic Block Copolymers on the Aggregation State of Nystatin , J. Contr. Release, 2004: 95: 161-171.
20.
Kabanov, A.V. , Chekhonin, V.P., Alakhov, et al. The Neuroleptic Activity of Haloperidol Increases After Its Solubilization in Surfactant Micelles: Micelles as Microcontainers for Drug Targeting, FEBS Lett. , 1989: 258: 343-345.
21.
Saettone, M.F. , Giannaccini. B., Delmonte, G., et al. Solubilization of Tropicamide by Poloxamers: Physicochemical Data and Activity Data in Rabbits and Humans, Int. J. Pharm., 1988: 43: 67-76.
22.
Molpeceres, J., Guzman, M., Bustamante, P. and Aberturas, M.D.Exothermic-Endothermic Heat of Solution Shift of Cyclosporin as Related to Poloxamer 188 Behavior in Aqueous Solutions , Int. J. Pharm., 1996: 130: 75-81.
23.
Saito, Y. and Sato, T.Effects of Inorganic Salts on Solubilization of Estriol in an Aqueous Solution of Poly(Ethylene Oxide)/Poly(Propylene Oxide)/ Poly(Ethylene Oxide) Triblock Copolymer, Drug Dev. Ind. Pharm., 1988: 24: 385-388.
24.
Exner, A.A. , Krupka, T.M., Scherrer, K. and Teets, J.M.Enhancement of Carboplatin Toxicity by Pluronic Block Copolymers, J. Contr. Release, 2005: 106: 188-197.
25.
Wang, Y.Z., Li, Y.Z., Han, L.M., Sha, X.Y. and Fang, X.L.Difunctional Pluronic Copolymer Micelles for Paclitaxel Delivery: Synergistic Effect of Folate-mediated Targeting and Pluronic Mediated Overcoming Multidrug Resistance in Tumor Cell Lines, Int. J. Pharm., 2007: 337: 63-73.
26.
Gao, Y., Li, L.B. and Zhai, G.Preparation and Characterization of Pluronic/ TPGS Mixed Micelles for Solubilization of Camptothecin, Colloids Surf. B Biointerfaces, 2008: 64: 194-199.
27.
Fang, J., Hsu, S., Leu, Y. and Hu, J.Delivery of Cisplatin from Pluronic Co-polymer Systems: Liposome Inclusion and Alginate Coupling, J. Biomater. Sci. Polym. Ed., 2009: 20: 1031-1047.
28.
Danson, S., Ferry, D., Alakhov, V., et al. Phase I Dose Escalation and Pharmacokinetic Study of Pluronic Polymer-Bound Doxorubicin (SP1049C) in Patients with Advanced Cancer, British J. Cancer, 2004: 90: 2085-2091.
29.
Park, E.K., Lee, S.B. and Lee, Y.M.Preparation and Characterization of Methoxy Poly(Ethylene Glycol)/Poly(ε-Caprolactone) Amphiphilic Block Copolymeric Nanospheres for Tumor-specific Folate-Mediated Targeting of Anticancer Drugs, Biomaterials, 2005: 26: 1053-1061.
30.
Higuchi, T.Mechanisms of Sustained Action Mediation. Theoretical Analysis of Rate of Release of Solid Drugs Dispersed in Solid Matrices, J. Pharm. Sci., 1963: 52: 1145-1149.
31.
Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P. and Peppas, N.A.Mechanisms of Solute Release from Porous Hydrophilic Polymers, Int. J. Pharm., 1983 : 15: 25-35.
32.
Sezgin, Z., Yuksel, N. and Baykara, T.Preparation and Characterization of Polymeric Micelles for Solubilization of Poorly Soluble Anticancer Drugs, Eur. J. Pharm. Biopharm. , 2008: 64: 261-268.
33.
Maeda, H.The Enhanced Permeability and Retention (EPR) Effect in Tumor Vasculature: The Key Role of Tumor-selective Macromolecular Drug Targeting, Adv. Enzyme Regul., 2001: 41: 189-207.
34.
Gao, J. , Ming, J., He, B., et al. Preparation and Characterization of Novel Polymeric Micelles for 9-Nitro-20(S)-Camptothecin Delivery, Eur. J. Pharm. Sci., 2008: 34: 85-93.
35.
Liu, S.Q. , Tong, Y.W. and Yang, Y.Y.Incorporation and In Vitro Release of Doxorubicin in Thermally Sensitive Micelles Made from Poly(N-Isopropylacrylamide-co-N,N-Dimethylacrylamide)-b-Poly(D,L-Lactide-co-Glycolide) with Varying Compositions, Biomaterials, 2005 : 26: 5064-5074.
36.
Lee, H., Soo, P.L., Liu, J., Butler, M. and Allen, C. ( 2007). Polymeric Micelles for Formulation of Anti-cancer Drugs , In: Amiji, M.M. (ed.), Nanotechnology for Cancer Therapy, New York, CRC Press, pp. 317-355.
