curcumin nanoparticles_1599661643.pptx

education lecture

1. Ministiry of higher Education and Scientific Research University of Babylon College of pharmacy Graduation progect Curcumin nanoparticles:physico-chemical fabrication and its in vitro efficacy against human pathogens. Submitted to: Dr.Tamadhur By: دعاءصادق علي مريم جاسم حسن

2. Introduction: Curcumin (curcumin-I) is the active ingredient of the dietary spiceturmeric (Curcuma longa, Family-Zingiberaceae) and has been consumed for medicinal purposes for thousands of years. The other curcuminoids present in turmeric are demethoxycurcumin (curcumin-II), bisdemethoxycurcumin (curcumin-III). Curcumin has wide range of applications such as anti-bacterial activity, anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, anti-proliferative, wound healing, anti-nociceptive, antiparasitic, anti-malarial, diabetes, obesity, neurologic, psychiatric disorders and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys, and gastrointestinal and cardiovascular systems.

3. Methods of preparation: • Coacervation techniques • Nanoprecipitation method • Spray drying method • Single emulsion method • Solvent evaporation method • Microemulsion • Wet milling method • Thin film hydration method • Solid dispersion method • Emulsion polymerization method • Fessi method • Ionic gelation method • Ultrasonication • Antisolvent precipitation method

4. Nanoprecipitation method: In this method, desired polymer is suspended in the suitable solvent to form polymeric solution and herbal drug (curcumin) is added into it. After that this drug- polymer solution is added into water under continuous stirring which results in precipitation. After that the solvent is allowed to evaporate by hot air flow. Spray drying resulted in the formation of drugs in the amorphous state, which may get partially crystallized during processing. In this method of synthesis, curcumin and polymer are dissolved in same solvent or mixture of solvents.

5. Physicochemical Properties: The chemical formula of CUR is C21H20O6, with IUPAC nomenclature of [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] and molecular weight of 368.38 Da. CUR displays keto-enol tautomerism with two isomer forms, enol form, and β-diketo form. The predominant isomer depends on the nature of solvent. In acidic and neutral solution, the keto form will predominate; while in alkaline medium, the stable enol form will predominate; The enol form is more stable when compared to diketo form by 7.75 kcal/mol, due to the presence of strong internal hydrogen bond and extended conjugation along the molecule in the stable enol form. CUR has a log P value of 2.5, allowing it to diffuse readily across cellular membranes .CUR is soluble in organic solvents such as dimethylsulfoxide, methanol, ethanol and chloroform, but insoluble in water. CUR exhibits two strong absorption bands: one between 410 and 430 nm in the visible region; and another at 265 nm in the ultraviolet region. The three pKa values of CUR were reported to be 7.8, 8.5, and 9.0, attributed by the dissociation of enolic proton and two phenolic protons in CUR. The estimation of pKa values is based on Nuclear Magnetic Resonance (NMR) and absorption spectrometry

6. chemical composition of curcumin Molecular Formula: IC21H20O6 or C21H20O6 Synonyms: curcumin 458-37-7 Diferuloylmethane Natural yellow 3 Turmeric yellowMolecular Weight: 368.4 g/mol

7. Curcumin is a phytopolylphenol pigment isolated from the plant Curcuma longa, commonly known as turmeric, with a variety of pharmacologic properties. Curcumin blocks the formation of reactive-oxygen species, possesses anti-inflammatory properties as a result of inhibition of cyclooxygenases (COX) and other enzymes involved in inflammation; and disrupts cell signal transduction by various mechanisms including inhibition of protein kinase C. These effects may play a role in the agent's observed antineoplastic properties, which include inhibition of tumor cell proliferation and suppression of chemically induced carcinogenesis and tumor growth in animal models of cancer. (NCI04)

8. In vivo and in vitro studies have demonstrated curcumin's ability to inhibit carcinogenesis at three stages: tumor promotion, angiogenesis and tumor growth . Curcumin suppresses mitogen-induced proliferation of blood mononuclear cells, inhibits neutrophil activation and mixed lymphocyte reaction and also inhibits both serum-induced and platelet derived growth factor (PDGF)-dependent mitogenesis of smooth muscle cells. It has also been reported to be a partial inhibitor of protein kinase. The other salient feature of turmeric/curcumin is that despite being consumed daily for centuries in Asian countries, it has not been shown to cause any toxicity(PMID

9. Curcumin nanomedicine: A road to cancer therapeutics Abstract : Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment.

10. CURCUMIN NANOFORMULATIONS: For the past few decades, nanoparticle technology has been widely employed in medicine, including for cancer therapy As drug nanocarriers, nanoparticles possess several attractive features: (i) improved encapsulation or solubilization of therapeutic drugs for protective and targeted delivery, (ii) high surface to volume ratio enable modifications to surface functional groups in order to obtain extensive stabilization and internalization, (iii) biocompatibility, superior pharmacokinetics and minimal clearance from body, and (iv) controlled, stimuli responsive, remote actuation and on demand drug release properties The use of curcumin in cancer treatment has limitations because of its low solubility, poor tissue absorption, rapid metabolism and rapid systemic elimination. Recent work has focused on improving the stability of curcumin to facilitate clinical application.

11. Approaches to improve the bioavailability of curcumin: T he main problem of clinical use of this dramatic phytochemical is its low solubility in water and hence  in vivo  bioavailabality. Unlike water, curcumin is soluble in organic solutes such as dimethyl solfoxide, ethanol and acetone. For this reason, curcumin tissue stability is short and thereafter it has low bioactivity. Measuring the plasma and urine content of curcumin showed that very low amount was absorbed by alimentary system which is not enough to be used as therapeutic purposes (Wahlström and Blennow, 1978).). A powerful strategy to overcome the problem of low absorption is blocking the decomposition and fast metabolism together with precise targeted delivery of curcumin toward the tissues. For example, the compounds including nanoparticles, micelles, liposomes, nanoemulsions, curcumin conjugates and its analogs were designed to enhance the time of curcumin maintenance in blood, tissue permeability as well as its resistance against catabolic processes .

12. Dendrosomal Nano-Curcumin; the last stable innovative compound of curcumin: Dendrosomes are defined as polymeric nano-carriers derived from oleic acid which initially were synthesized by Sarboluki et al. in 2000, through self-assembly of spherical-structured co-polymers. The prominent advantages of dendrosomes are long-time stability, non-toxicity, having no electitical charges, high biological disintegrativity and facility of production Dendrosomal nano-curcumin (DNC) is one of the most successful compounds showing significant cellular absorption and also anti-tumor effects. The present overview of newest applicable strategies for curcumin-based therapy and their clinical potential usefulness has the emphasis on DNC . By taking the advantage of dendrosomes in delivery of genes into alive cells, a strategy was offered based on the use of dendrosome to carry insoluble curcumin in side cancer cells. Studies showed that beside the efficient delivery of curcumin, dendrosome nanoparticles affect cancer cells rather than normal ones. recently (2012) reported that dendrosomal nano-curcumin suppresses cancer cell proliferation  in vitro  and  in vivo  .These data confirmed high solubility of dendrosome encapsulated curcumin and its significant anti-tumor effect on different cell lines..

13. They investigated the effects of nanocurcumin in bladder cancer cell lines. They found that nanocurcumin exerts its function through inhibition of pluripotency genes’ activity . Since the oncogenicity of pluripotency genes (Oct 4, SOX2 and NANOG) were previously declared, targeting these genes is considered now as a new successful approach for cancer treatment. Data showed that curcumin suppressed Oct4, SOX2 and NANOG in bladder cell lines suggesting therapeutic effect of nano-particle in bladder cancer. Tahmasebi et al., (2014) found that dentrosomal curcumin’s suppression effect on pluripotency genes is mediated by activation of miRNA-145 (Mirgani et al., 2014). In another study it was showed that dentrosomal curcumin suppresses the expression of the anti-apoptotic gene, BCL2 and enhances the expression of the pro-apoptotic gene, Bax in dose- and time-dependent manner (Abedi and Babaei, 2015).

14. The results showed that different concentrations of dendrosomal curcumin inhibit metastasis. Investigations in order to find the underlying molecular mechanisms showed that metastasis inhibitory effect of curcumin is through NF-kB repression and consequent down-regulation of MMP-2, VEGF and COX2. Recent additional studies declared that dendrosomal curcumin enhances the expression of long non-coding RNA MEG3 via activation of epi-miRs in hepatocellular carcinoma and glioblastoma cells. MEG3 is a tumor suppressor long non-coding RNA whose promoter is methylated in many human cancers. In fact, dendrosomal nano-curcumin causes alteration in methylation status of genome, induced by epi- miRs such as miR-29a and miR-185 which target DNMT3A , DNMT3B and DNMT1 genes. These finding imply that dendrosomal curcumin may alter the methylation status of genome by which some promoters of tumor suppressor genes become hyperactivated. This fact has potentiality of being used in “epigenetic therapy” .

15. From last few decades, the investigations have explored the curative effects of curcumin in endometrial and ovarian cancer cells on the negative controllers of activated STAT-3 like SHP-1, SHP-2, SOCS and PIA. Various polymeric nano formulations of curcumin were synthesized by crosslinking of N-isopropyl acrylamide, N-vinyl-2-pyrrolidone, and poly (ethylene glycol) monoacrylate and studied its anti-proliferative activity against pancreatic cancer cells and amended results were obtained in the case of polymer loaded nanoparticles as compared to native curcumin .

16. References 1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–36.  2. Tan W, Lu J, Huang M, et al. Anti-cancer natural products isolated from Chinese medicinal herbs. Chin Med. 2011;6:27.  3. Treasure J. Herbal medicine and cancer: an introductory overview. Semin Oncol Nurs. 2005;21:177–83.  4. Ahmad A, Sakr WA, Rahman KM. Novel targets for detection of cancer and their modulation by chemopreventive natural compounds. Front Biosci (Elite Ed) 2012;4:410–25.  5. Gullett NP, Ruhul Amin AR, Bayraktar S, et al. Cancer prevention with natural compounds. Semin Oncol.  6. Nobili S, Lippi D, Witort E, et al. Natural compounds for cancer treatment and prevention. 

17. Thank you