Formulation Of Curcumin Research Articles

Topical application of curcumin regulates the angiogenesis in diabetic-impaired cutaneous wound.

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin-induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re-epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor-κB (NF-κB) signalling pathway. However, no significant effects on macrophage polarization and re-epithelialization were observed in the curcumin-treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis-promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation. SIGNIFICANCE OF THE STUDY: Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti-inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high-dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re-emphasize the proangiogenic potential of curcumin in diabetic wound environment.

Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats.

Curcumin (CUR) is a major component of turmeric Curcuma longa, which is often used in food or as a dietary supplement. The purpose of this preclinical study is to investigate the acute pharmacokinetic and pharmacodynamic (PK/PD) profiles of two commercially marketed CUR products (GNC and Vitamin Shoppe) and a CUR powder from Sigma in female rats. Plasma samples were collected at specific time points and analyzed for CUR and its metabolite curcumin-O-glucuronide. RNA was extracted from leukocytes and analyzed for the expression of Nrf2-mediated antioxidant genes Nrf2, Ho-1, and Nqo1 by qPCR as selected PD markers. CUR PK was characterized by a 2-compartment model (2CM) after intravenous (IV) or oral administrations. Compared to IV CUR, the absolute bioavailability (F) of CUR for GNC (GC) is 0.9%, Vitamin Shoppe (VC) is 0.6% and Sigma (SC) is 3.1%. Pharmacodynamically, all three formulations showed induction of antioxidant Nrf2, Ho-1 and Nqo1 gene expression in rat leucocytes. PK/PD modeling of CUR's effect on antioxidant gene expression was well captured by an indirect response model. Physiologically based PK modeling and simulation using GastroPlus described the observed PK data reasonably well. In summary, our current study shows that the absolute oral bioavailability of the parent CUR was very low for all three formulations. However, despite the low CUR plasma concentrations, all three oral CUR formulations displayed PD response in the induction of Nrf2-mediated antioxidant genes, suggesting the potential of oral CUR contributing to the overall health beneficial effects of oral CUR.

Single-step coprecipitation and coating to prepare curcumin formulations by supercritical fluid technology

Common strategies to improve the dissolution properties of hydrophobic drug compounds include the preparation of composites with hydrophilic excipients and/or size reduction. However, nanoparticles have poor flowability and difficult handling. Therefore, this work aims to demonstrate the single-step improvement of dissolution and flow properties of pharmaceutical formulations. Coprecipitates of curcumin and poly (vinyl pyrrolidone) (guest particles) are simultaneously produced and coated onto microcrystalline cellulose (MCC, 175 μm), corn starch (15 μm) and lactose (< 5 μm) (host particles), by combining the Supercritical Antisolvent process with two different configurations of fluidized bed (tapered bed and stirred vessel). Experiments were performed at 40 °C, 9−12 MPa, 2.5–30.0 % guest/host mass ratio and stirrer speed varying from 400 to 1200 rpm. SEM images demonstrated that nanoparticles of coprecipitates were obtained while DSC results showed that they were amorphous, explaining the remarkable improvement in dissolution achieved. Free-flowing powder was obtained when MCC was used.

Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment.

The aim of this study was to investigate the efficacy and safety of curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC*; Diabec®-AlfaIntes, Italy) for the treatment of macular edema (ME) from uncommon etiologies. We conducted retrospective interventional case series, reviewing the medical records of patients referred to the Eye Center, Humanitas Hospital, Bergamo due to persistent ME related to uncommon causes and treated by oral administration of CHC. The main outcomes assessed were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the presence of intraretinal and/or subretinal fluid (SRF). Only patients with a minimum follow-up (f/u) of 6 months were included. The occurrence of any adverse effect was registered. Thirty-one eyes of 30 patients were included, with a mean f/u of 8.32 ± 1.77 months. Of them, 9 patients (10 eyes) were affected by postoperative ME and 21 by chronic central serous chorioretinopathy. Median BCVA significantly improved after treatment, changing from 0.3 [0.16-0.5] to 0.1 [0-0.3] logarithm of the minimum angle of resolution (P < .001). Also CMT was significantly improved, as it decreased from 400 [364-438] μm before treatment to 280 [242-307] μm at the last f/u visit (P < .001). The complete absorption of intraretinal/SRF was detected in 23 of 31 eyes (74%) at the final f/u. No adverse effects were registered. In conclusion, treatment with CHC was effective and safe for eyes affected by ME of various uncommon etiologies, resulting in significant improvement of both functional and anatomical outcomes, with the complete resolution of the edema in the majority of cases (74%).

Optimization for microbial incorporation and efficiency of photodynamic therapy using variation on curcumin formulation.

A mixture of curcuminoids: curcumin, desmethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are named natural curcumin. It is a lipophilic photosensitizer (PS) highly soluble in an organic solvent such as dimethyl sulfoxide (DMSO). Curcumin is a PS used for microbial inactivation using photodynamic action. However, this solvent has high cytotoxicity and is unavailable in formulations for clinical use. This study aimed to investigate the interactions of curcuminoids syrup with Streptococcus sp., a gram-positive coccus and one of the major pharyngeal pathogens, responsible for diseases such as pharyngitis. Bacteria were incubated with curcuminoids (natural curcumin, synthetic, DMC, BDMC) at 37 °C in formulations: 1) syrup (water + sucrose) 2) solution alcohol + DMSO. Was centrifuged, and the supernatant collected for absorbance analysis. The results obtained correlating the absorbance with the supernatant to the absorbance of the default concentration. A study of microbial metabolism by growth curve was carried out to justify the result. The incorporation of curcumin in syrup is superior to alcohol/DMSO solution by microorganisms. Curcumin incorporation by S. mutans, S. pyogenes, isolated bacteria was 24, 26, 27 % in syrup and 10, 13, 5 % in alcohol/DMSO, respectively. Also, the presence of carbohydrate in a solution can activate the bacterial metabolism, getting better uptake results and photodynamic inactivation to natural curcumin and DMC. Such finds care optimizes the use of curcumin without complications generated by the solvent.

Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa.

Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women.

Formulation of Curcumin as Natural Dye on Polyester

Turmeric is perennial herbs that has been used for centuries as natural dye in the Asia. It contains curcumin that generate yellow to orange color. Unfortunately, curcumin is considered as fugitive dyes because its color strength will diminish within times. In order to strengthen the color of curcumin, some additives are added into dye formulation. In this research, turmeric juice was extracted from turmeric without adding any organic solvents. The juice was then mixed with mordant and emulsifier to produce dye solution. Alum and lime juice were used as synthetic and natural mordant, respectively. Tween 80 was used as emulsifier. The polyester was soaked in the dye solution for overnight. The color strength (K/S), the color wash fastness, and the color coordination of the dyed polyester were investigated. The research shows that the ratio of turmeric juice to mordant of 2:1 (without any emulsifiers) gave the best color strength and color fastness.

Curcumin-Loaded Mesoporous Silica Particles as Wound-Healing Agent: An In vivo Study.

Background:Curcumin likely has wound-healing properties, but its poor pharmacokinetic attributes inhibit its potential. To overcome these limitations, a novel nanoformulation was previously developed, wherein curcumin was loaded into mesoporous silica particles.Objectives:The objective of the study is to assess the efficiency of this nanocurcumin formulation as a wound-healing agent in an animal model.Materials and Methods:Curcumin was loaded onto mesoporous silica particles. Eighteen healthy, test-naive male Wistar rats were randomly separated into two groups of 9: Group 1 (control) rats were treated topically with a standard drug (sulfadiazine) and Group 2 with 1% curcumin formulation. A circular excision wound was made, and topical application was performed twice a day. The excision diameters were measured on days 3, 6, 9, 12, 15, 18 and 21 of treatment. Three rats from each group were sacrificed on days 7, 14 and 21, and a cross-section from skin specimen in the excision injury was obtained for histological assessment of inflammation, angiogenesis, fibroblast proliferation, presence of collagen and reepithelization.Results:Wound contraction percentage in rats treated with curcumin nanoformulation was nonsignificantly higher than that in the control group (P > 0.05). In both groups, inflammatory reactions considerably reduced by day 21 of treatment, the angiogenesis process was almost complete by day 7, fibroblast proliferation noticeably rose by day 14, and a high degree of wound reepithelization was achieved by day 21, with no significant differences between the groups. Interestingly, by day 21, the level of collagen significantly increased in curcumin nanoformulation-treated rats compared with those treated with sulfadiazine.Conclusions:Curcumin nanoformulation likely enhanced wound repair by inhibiting the inflammatory response, stimulating angiogenesis, inducing fibroblast proliferation as well as enhancing reepithelization and synthesis of collagen. Therefore, the curcumin nanoformulation used in this study may have potential as a wound-healing ethnomedicine.

Combination treatment of berberine and solid lipid curcumin particles increased cell death and inhibited PI3K/Akt/mTOR pathway of human cultured glioblastoma cells more effectively than did individual treatments.

The treatment of glioblastoma is challenging for the clinician, due to its chemotherapeutic resistance. Recent findings suggest that targeting glioblastoma using anti-cancer natural polyphenols is a promising strategy. In this context, curcumin and berberine have been shown to have potent anti-cancer and anti-inflammatory effects against several malignancies. Due to the poor solubility and limited bioavailability, these compounds have limited efficacy for treating cancer. However, use of a formulation of curcumin with higher bioavailability or combining it with berberine as a co-treatment may be proving to be more efficacious against cancer. Recently, we demonstrated that solid lipid curcumin particles (SLCPs) provided more bioavailability and anti-cancer effects in cultured glioblastoma cells than did natural curcumin. Interestingly, a combination of curcumin and berberine has proven to be more effective in inhibiting growth and proliferation of cancer in the liver, breast, lung, bone and blood. However, the effect of combining these drugs for treating glioblastoma, especially with respect to its effect on activating the PI3K/Akt/mTOR pathways has not been studied. Therefore, we decided to assess the co-treatment effects of these drugs on two different glioblastoma cell lines (U-87MG and U-251MG) and neuroblastoma cell lines (SH-SY5Y) derived from human tissue. In this study, we compared single and combination (1:5) treatment of SLCP (20 μM) and berberine (100 μM) on measures of cell viability, cell death markers, levels of c-Myc and p53, along with biomarkers of the PI3K/Akt/mTOR pathways after 24-48 h of incubation. We found that co-treatment of SLCP and berberine produced more glioblastoma cell death, more DNA fragmentation, and significantly decreased ATP levels and reduced mitochondrial membrane potential than did single treatments in both glioblastoma cells lines. In addition, we observed that co-treatment inhibited the PI3K/Akt/mTOR pathway more efficiently than their single treatments. Our study suggests that combination treatments of SLCP and berberine may be a promising strategy to reduce or prevent glioblastoma growth in comparison to individual treatments using either compound.

Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules.

BackgroundBladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methodsA dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.ResultsEncapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 µg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.ConclusionThese results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.

Formulation and evaluation of Metformin Hydrochloride-loaded Curcumin–Lycopene Niosomes

Curcumin and lycopene, both are naturally occurring potent antioxidants which can be used in the treatment of oxidative stress. The biological sources to obtain curcumin and lycopene are curcuma longa and Solanum lycopersicum, respectively. The aim of this research study is to develop curcumin–lycopene conjugate-based biguanide niosomes. Span 60 as non-ionic surfactant and cholesterol as a stabilizer were used for the preparation of metformin hydrochloride-loaded niosomes by the ethanol injection method. This research dealt with the composition, formulation, evaluation and optimization of niosomes. The particle size and polydispersity index were found to be in the range from 139.6 to 509 and 0.152 to 0.541 nm, respectively. The entrapment efficiency and drug loading capacity were observed in the range of 40.43–79.02 and 26.954 to 78.17%, respectively. The in vitro drug release studies showed the sustained release of drug in all formulations up to the period of 24 h. Kinetic analysis of in vitro drug release studies showed that when the ratio of Span 60 and cholesterol is 1:1.5 and 1:2, the formulations followed first-order kinetics. When the ratio changed to 1:1, the formulation followed the Korsmeyer–Peppas model and finally at the ratio of 1.5:1 and 2:1, formulations followed the Higuchi kinetics and Hixson–Crowell kinetics, respectively. Formulation S2 is concluded as an optimized formulation on the basis of all evaluation parameters.

Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and 1H NMR spectra assays showed that curcumin/hydroxypropyl-β-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29–30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 h in vitro drug release test. Curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

Turmeric/curcumin

Curcumin is the primary curcuminoid present in the turmeric plant, Curcuma longa, and gives turmeric its orange-yellow color. The names “turmeric” and “curcumin” are often used interchangeably, especially for the spice used in cooking. Turmeric extracts and curcumin are used primarily for osteoarthritis (OA) and inflammatory conditions. They also may have activity in diabetes, obesity, and cardiovascular diseases. Curcumin has anti-inflammatory activity via inhibition of arachidonic acid, lipoxygenase, COX, nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukins. In a study of knee OA, 30 mg of curcumin extract three times daily decreased COX-2 secretion into synovial fluid, similar to the effect of 25 mg of diclofenac three times daily. In another study of knee OA, serum levels of Coll2-1, a cartilage-specific biomarker, were significantly reduced. Clinical trials demonstrating benefit have used 1,000–1,500 mg per day in divided doses. The oral bioavailability of turmeric/curcumin may be low, so products that contain black pepper extracts or other compounds as absorption enhancers are preferred. The most common adverse effects are GI discomfort and nausea. Human studies have shown good tolerance even with higher dosages. Curcumin inhibits platelet aggregation in vitro and in vivo, so patients taking antithrombotic agents such as warfarin or clopidogrel should use this botanical cautiously. Multiple small studies have evaluated curcumin and related compounds for treatment of OA and rheumatoid arthritis (RA), alone or in combination with other natural products. Although some studies were placebo controlled, others compared curcumin with NSAIDs. An Iranian study of 40 participants with knee OA compared treatment with 1,500 mg of curcuminoids per day in three divided doses with placebo for 6 weeks. Treatment with curcuminoids resulted in greater improvements on standard OA assessment tools, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne’s pain functional index, and visual analogue scale (VAS), with few adverse effects. Pain and physical function also improved, but not stiffness. An Indian trial1Amalraj A. et al.J Med Food. 2017; 20: 1022-1030Crossref PubMed Scopus (62) Google Scholar randomized 36 participants with RA into three groups to receive 250 mg or 500 mg of curcumin or placebo twice daily for 90 days. The active treatment groups had significant improvement in their clinical symptoms at study end. Favorable changes in disease markers also occurred, including the erythrocyte sedimentation rate, C-reactive protein levels, and rheumatoid factor values. A 2018 Indian study2Karlapudi V. et al.J Med Food. 2018; 21: 511-520Crossref PubMed Scopus (9) Google Scholar of 105 patients with OA evaluated a combination curcumin product versus placebo in a 90-day trial that demonstrated improvements in pain, physical function, and quality of life. A noninferiority trial of 367 participants with OA compared 1,500 mg of curcumin extract daily to 1,200 mg of ibuprofen daily for 4 weeks. The WOMAC total, pain, stiffness, and function scores were similar between the curcumin and ibuprofen groups, with about two-thirds of participants rating themselves as “improved” on the global assessment. Curcumin-treated patients had less abdominal pain. An OA trial of 120 participants evaluated several natural products. Patients were randomized to receive 500 mg of curcumin extract, 750 mg of glucosamine sulfate, curcumin extract/glucosamine sulfate, or placebo twice daily for 42 days. The VAS pain scores were reduced from baseline, with the greatest reduction in the curcumin extract group. The WOMAC scores were also improved in the curcumin extract group. Improvements from baseline were noted with glucosamine, but less than those with curcumin. Evidence for curcumin/turmeric is promising given its safety, and it may be an option for patients with mild OA symptoms. Inform patients that the curcumin formulations used in studies may not be widely available. Products containing compounds such as black pepper extract are recommended and should be taken with meals with fats or oils to enhance absorption.

Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is associated with reduced lung compliance and hypoxemia. Curcumin exhibits potent anti-inflammatory properties but has poor solubility and rapid plasma clearance. To overcome these physiochemical limitations and uncover the full therapeutic potential of curcumin in lung inflammation, in this study we utilized a novel water-soluble curcumin formulation (CDC) and delivered it directly into the lungs of C57BL/6 mice inoculated with a lethal dose of Klebsiella pneumoniae (KP). Administration of CDC led to a significant reduction in mortality, in bacterial presence within blood and lungs, as well as in lung injury, inflammation, and oxidative stress. The expression of Klebsiella hemolysin gene; TNF-α; IFN-β; nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; hypoxia-inducible factor 1/2α; and NF-κB were also decreased following CDC treatment, suggesting modulation of the inflammasome complex and hypoxia signaling pathways as an underlying mechanism by which CDC reduces the severity of pneumonia. On a cellular level, CDC led to diminished cell death, improved viability, and protection of human lung epithelial cells in vitro. Overall, our studies demonstrate that CDC administration improves cell survival and reduces injury, inflammation, and mortality in a murine model of lethal gram-negative pneumonia. CDC, therefore, has promising anti-inflammatory potential in pneumonia and likely other inflammatory lung diseases, demonstrating the importance of optimizing the physicochemical properties of active natural products to optimize their clinical application.-Zhang, B., Swamy, S., Balijepalli, S., Panicker, S., Mooliyil, J., Sherman, M. A., Parkkinen, J., Raghavendran, K., Suresh, M. V. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.

Is curcumin bioavailability a problem in humans: lessons from clinical trials

ABSTRACTIntroduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principal component of turmeric is curcumin and its efficacy has been advocated in various in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem.Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated the pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies.Expert opinion: The therapeutic potential of curcumin, as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailability in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin, in combination with other compounds or as formulations, has shown enhanced bioavailability. Hence, bioavailability is not a problem in the curcumin-mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases.

Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects.

Turmeric is a curry spice that originated from India, which has attracted great interest in recent decades because it contains bioactive curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione), a lipophilic polyphenol may work as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent as suggested by several in vitro, in vivo studies and clinical trials. However, poor aqueous solubility, bioavailability, and pharmacokinetic profiles limit curcumin’s therapeutic usage. To address these issues, several curcumin formulations have been developed. However, suboptimal sample preparation and analysis methodologies often hamper the accurate evaluation of bioactivities and their clinical efficacy. This review summarizes recent research on biological, pharmaceutical, and analytical aspects of the curcumin. Various formulation techniques and corresponding clinical trials and in vivo outcomes are discussed. A detailed comparison of different sample preparation (ultrasonic, pressurized liquid extraction, microwave, reflux) and analytical (FT-IR, FT-NIR, FT-Raman, UV, NMR, HPTLC, HPLC, and LC-MS/MS) methodologies used for the extraction and quantification of curcuminoids in different matrices, is presented. Application of optimal sample preparation, chromatographic separation, and detection methodologies will significantly improve the assessment of different formulations and biological activities of curcuminoids.

Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0–fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.

Green formulation of curcumin loaded lipid-based nanoparticles as a novel carrier for inhibition of post-angioplasty restenosis.

Restenosis is one of the major complications affecting outcomes of percutaneous coronary interventions. The aims of this study were to formulate curcumin (CUR) nanoparticles by using only lipidic ingredients in the absence of any organic solvent and to determine key formulation parameters using 2-level factorial design. CUR nanoparticles were prepared using triglyceride and egg phosphatidylcholine (EPC) by high-pressure homogenization (HPH) and fully characterized regarding drug loading, particle size, zeta potential, stability, drug release profile, conductivity, viscosity, refractive index, stability, morphology and FTIR analysis. The efficacy of CUR nanoparticles in inhibiting restenosis was investigated in a rat carotid artery model. Balloon-injured rats were randomly assigned to two control (saline and empty carrier) groups and CUR nanoparticle treated group. Arterial restenosis was assessed by histomorphometric, immunohistochemical and CT angiography analyses. Optimized CUR nanoparticles with almost 70% drug entrapment, an average particle size of 58 nm, PDI < 0.2, spherical nanostructures and sustained release profile were prepared. In morphometric analysis, neointimal area and neointima/media ratio significantly decreased in the animal group received CUR nanoparticles compared with control groups. Expression of Ki67 was markedly lower in the CUR nanoformulation group. CT angiograms confirmed patency of the artery in this group. These results suggest that the new strategy of intramural delivery of CUR lipid-based nanoparticles can be considered as a novel approach to prevent neointimal hyperplasia.

Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues.

The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD. The bioavailability of curcumin is negligible due to its poor aqueous solubility. The purpose of this work is to develop an aqueous nanomicellar drop formulation of curcumin (CUR-NMF) for back of the eye delivery utilizing hydrogenated castor oil (HCO-40) and octoxynol-40 (OC-40) to treat AMD. A full factorial design was performed with JMP software analysis to optimize the formulation size, polydispersity index (PDI), entrapment efficiency, loading, and precipitation. MTT and LDH assays on human retinal pigmented epithelial (D407) cells revealed that 5-10μM CUR-NMF dose is safe for ophthalmic use. Furthermore, CUR-NMF exhibited significant protection of retinal (D407) cells against H2O2-induced oxidative stress. In vitro drug release kinetics suggested a sustained drug release profile indicating a long-term protection ability of CUR-NMF against oxidative stress to retinal cells. In addition, an ELISA suggested that CUR-NMF significantly reduces vascular endothelial growth factor (VEGF) release in D407 cell line, hence diminishes the risk of angiogenesis. Collectively, these results suggest that the proposed CUR-NMF can be tremendously effective in treating both types of AMD.

Chemopreventive Effect of Phytosomal Curcumin on Hepatitis B Virus-Related Hepatocellular Carcinoma in A Transgenic Mouse Model

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), a leading cause of cancer mortality worldwide. Hepatitis B X protein (HBx) and pre-S2 mutant have been proposed as the two most important HBV oncoproteins that play key roles in HCC pathogenesis. Curcumin is a botanical constituent displaying potent anti-inflammatory and anti-cancer properties without toxic side effects. Phytosomal formulation of curcumin has been shown to exhibit enhanced bioavailability, improved pharmacokinetics, and excellent efficacy against many human diseases. However, effectiveness of phytosomal curcumin for HCC treatment remains to be clarified. In this study, we evaluated chemopreventive effect of phytosomal curcumin on HBV-related HCC by using a transgenic mouse model specifically expressing both HBx and pre-S2 mutant in liver. Compared with unformulated curcumin, phytosomal curcumin exhibited significantly greater effects on suppression of HCC formation, improvement of liver histopathology, decrease of lipid accumulation and leukocyte infiltration, and reduction of total tumor volume in transgenic mice. Moreover, phytosomal curcumin exerted considerably stronger effects on activation of anti-inflammatory PPARγ as well as inhibition of pro-inflammatory NF-κB than unformulated curcumin. Furthermore, phytosomal curcumin showed a comparable effect on suppression of oncogenic mTOR activation to unformulated curcumin. Our data demonstrated that phytosomal curcumin has promise for HCC chemoprevention in patients with chronic HBV infection.