Encapsulation of Curcumin in Pluronic Block Copolymer Micelles for Drug Delivery Applications

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.

[1]  L. Bromberg.  Polymeric micelles in oral chemotherapy. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[2]  B. E. Foreman,et al.  Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals , 2007, Acta Pharmacologica Sinica.

[3]  B. Aggarwal,et al.  Curcumin as "Curecumin": from kitchen to clinic. , 2008, Biochemical pharmacology.

[4]  Alexander V Kabanov,et al.  Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[5]  E. K. Park,et al.  Preparation and characterization of methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs. , 2004, Biomaterials.

[6]  Yujiang Fan,et al.  Preparation and characterization of novel polymeric micelles for 9-nitro-20(S)-camptothecin delivery. , 2008, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  Alexander V Kabanov,et al.  Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Ricky A. Sharma,et al.  Curcumin: the story so far. , 2005, European journal of cancer.

[9]  N. Melik-Nubarov,et al.  The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles , 1989, FEBS letters.

[10]  T. Higuchi.  MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[11]  Kazunori Kataoka,et al.  Block copolymer micelles as long-circulating drug vehicles , 1995 .

[12]  Abhishek Sahu,et al.  Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells. , 2008, Acta biomaterialia.

[13]  G. Zhai,et al.  Preparation and characterization of Pluronic/TPGS mixed micelles for solubilization of camptothecin. , 2008, Colloids and surfaces. B, Biointerfaces.

[14]  A. Exner,et al.  Enhancement of carboplatin toxicity by Pluronic block copolymers. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[15]  S. Takeoka,et al.  Loading of curcumin into macrophages using lipid-based nanoparticles. , 2008, International journal of pharmaceutics.

[16]  R. K. Chowdhary,et al.  Formulation of Benzoporphyrin Derivatives in Pluronics ¶ , 2003, Photochemistry and photobiology.

[17]  Yi Yan Yang,et al.  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. , 2005, Biomaterials.

[18]  S. Hsu,et al.  Delivery of Cisplatin from Pluronic Co-polymer Systems: Liposome Inclusion and Alginate Coupling , 2009, Journal of biomaterials science. Polymer edition.

[19]  D. Kerr,et al.  Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer , 2004, British Journal of Cancer.

[20]  M. R. Aberturas,et al.  Exothermic-endothermic heat of solution shift of cyclosporin a related to poloxamer 188 behavior in aqueous solutions , 1996 .

[21]  C. Allen,et al.  Polymeric Micelles for Formulation of Anti-Cancer Drugs , 2006 .

[22]  R. Lai,et al.  Micelles of poly(ethylene oxide)-b-poly(epsilon-caprolactone) as vehicles for the solubilization, stabilization, and controlled delivery of curcumin. , 2008, Journal of biomedical materials research. Part A.

[23]  Robert A Newman,et al.  Bioavailability of curcumin: problems and promises. , 2007, Molecular pharmaceutics.

[24]  Christine Allen,et al.  Nano-engineering block copolymer aggregates for drug delivery , 1999 .

[25]  Abhishek Sahu,et al.  Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells. , 2008, Biomacromolecules.

[26]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[27]  A. Singh,et al.  Multiple biological activities of curcumin: a short review. , 2006, Life sciences.

[28]  D. Chiappetta,et al.  Poly(ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: improved hydrosolubility, stability and bioavailability of drugs. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[29]  H. Maeda.  The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[30]  M. F. Saettone,et al.  Solubilization of tropicamide by poloxamers: physicochemical data and activity data in rabbits and humans , 1988 .

[31]  G. Feldmann,et al.  Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy , 2007, Journal of nanobiotechnology.

[32]  B. Aggarwal,et al.  Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. , 2009, The international journal of biochemistry & cell biology.

[33]  T. Baykara,et al.  Preparation and characterization of polymeric micelles for solubilization of poorly soluble anticancer drugs. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[34]  T. Sato,et al.  Effects of inorganic salts on solubilization of estriol in an aqueous solution of poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer. , 1998, Drug development and industrial pharmacy.

[35]  Xiaoling Fang,et al.  Difunctional Pluronic copolymer micelles for paclitaxel delivery: synergistic effect of folate-mediated targeting and Pluronic-mediated overcoming multidrug resistance in tumor cell lines. , 2007, International journal of pharmaceutics.

[36]  G. Kwon,et al.  The effects of Pluronic block copolymers on the aggregation state of nystatin. , 2004, Journal of controlled release : official journal of the Controlled Release Society.