Curcumin-phospholipid Complex Research Articles

Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin β-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex.

Curcumin is a natural acidic polyphenol extracted from turmeric with a wide range of biological and pharmacological effects. However, the application of curcumin for animal production and human life is limited by a low oral bioavailability. In this study, natural curcumin was prepared for the curcumin β-cyclodextrin inclusion complex (CUR-β-CD), curcumin solid dispersion (CUR-PEG-6000), and curcumin phospholipid complex (CUR-HSPC) using co-precipitation, melting, and solvent methods, respectively. Curcumin complex formations were monitored using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques via the shifts in the microscopic structure, molecular structure, and crystalline state. Subsequently, twenty-four female beagle dogs were randomly divided into four groups to receive unmodified curcumin and three other curcumin preparations. The validated UPLC–MS assay was successfully applied to pharmacokinetic and bioavailability studies of curcumin in beagle dog plasma, which were collected after dosing at 0 min (predose), 5 min, 15 min, 30 min, 40 min, 50 min, 1.5 h, 3 h, 4.5 h, 5.5 h, 6 h, 6.5 h, 9 h, and 24 h. The relative bioavailabilities of CUR-β-CD, CUR-PEG-6000, and CUR-HSPC were 231.94%, 272.37%, and 196.42%, respectively. This confirmed that CUR-β-CD, CUR-HSPC, and especially CUR-PEG-6000 could effectively improve the bioavailability of curcumin.

<p>Hybrid curcumin–phospholipid complex-near-infrared dye oral drug delivery system to inhibit lung metastasis of breast cancer</p>

Background: Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin–phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer.Methods: CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice.Results: CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.

Voyage into Curcumin Embedded Delivery Systems of Natural Polymers to Ameliorate Solubility and Bioavailability Limitations

The turmeric (Curcuma longa) plant, a perennial herb of the ginger family, is an agronomic crop in south and southeast tropical Asia. The rhizome is coined as the most useful part of the plant and a staple in all cooking and treatment of medicinal purposes include antioxidant, anti-viral, anti-bacterial, anti-fungal, anti-carcinogenic, anti-mutagenic and anti-inflammatory. It has a wide array of affinity to biological proteins and inhibits various kinases. Curcumin modulates the activity of several transcription factors, regulates the functioning of inflammatory enzymes, cytokines, adhesion molecules, and apoptic proteins. Recent preclinical and animal studies revealed the anti-proliferative, anti-invasive and antiangiogenic activity5,6. Clinically, Curcumin is proven to be safe while administering at larger doses, but due to poor aqueous solubility, quick systemic elimination, scanty tissue absorption and degradation at alkaline pH, which restrains its bioavailability, following strategies are used to enhance the bioavailability: (i) adjuvants like piperine which interferes with glucuronidation, (ii) liposomal curcumin, (iii) nanoparticles, (iv) Curcumin phospholipid complex and (v) structural analogues of curcumin. (VI) Micronisation and nanonisation (VII) self-microemulsifying drug delivery systems (SMEDDS), (vii) cyclodextrin inclusions, (IX) solid dispersions (X) Nanoemulsions, nanospheres, nanobeads, nanofibres7. The intention of this comprehension is to present a retrospective and prospective gist of applications of innovative delivery systems of Curcumin employed by the researchers to optimize Curcumin delivery using natural polymers with the objective of enhancing solubility and bioavailability, which might revolutionize the therapy of challenging chronic disorders of mankind.

Studies on the curcumin phospholipid complex solidified with Soluplus®.

With the purpose of developing a curcumin phospholipid complex (CPC) formulation with high performance, the CPC was prepared and solidified with Soluplus® in this study. Soluplus® was used as a carrier to solidify CPC. The structures of the CPC and curcumin phospholipid complex - Soluplus® solidified powder (CSP) - were also characterized by differential scanning electron microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffractometer, and flowability, in-vitro dissolution and oral bioavailability were also investigated. All analysis indicated that curcumin was completely converted from crystalline to amorphous state in solidified powder. The angle of repose calculated in flowability study indicated a marked improvement from 'cannot be measured' to '37°'. Meanwhile, the dissolution study showed that in phosphate buffer condition, the dissolution rate of CSP had released 76.34% in pH 6.8 and the 78.19% in pH 1.2. Furthermore, in pharmacokinetic study, significant (P<0.01) improvement of AUC0-∞ value was observed between CPC and CSP groups, and the results showed that AUC0-∞ value was increased from 205.84±50.46μgh/ml to 330.47μgh/ml. A simple and convenient solidifying process was used in this study, and the data suggested that this process not only could improve the flowability and dissolution of phospholipid complex, but also increased the oral bioavailability of curcumin.

The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6weeks. Subjects (n=120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1g/day of simple curcumin, the phospholipidated curcumin group received 1g/day of phospholipidated curcumin (containing 200mg of pure curcumin), and the control group received 1g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p<0.001), but in the phospholipidated curcumin group, elevation of PAB level was not significant (p=0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd.

The effect of curcumin (Curcuma longa L.) on circulating levels of adiponectin in patients with metabolic syndrome

In modern societies, metabolic syndrome (MetS) is a highly common disease, which is closely associated with the increased risk of cardiovascular disease (CVD). Metabolic syndrome is usually accompanied by low levels of adiponectin, which is a key regulator of insulin sensitivity and reduced inflammation of the tissue. Adiponectin also reduces systemic insulin resistance and predicts cardiovascular disease. Curcumin has several beneficial effects on risk factors of metabolic syndrome. This polyphenol can affect almost all components of metabolic syndrome including insulin resistance, hypertension and obesity. According to the low oral bioavailability of curcumin, several phospholipid-complex formulations have been developed to address this issue. The present study aims to evaluate the impact of unformulated curcumin and a phospholipid complex of curcumin on serum adiponectin in subjects with metabolic syndrome. Subjects (n = 120) with metabolic syndrome were randomly assigned to three groups which received capsules of phospholipidated curcumin (1 g/day), (n = 40), unformulated curcumin (n = 40) and placebo (n = 40) for a period of 6 weeks. The serum concentrations of adiponectin were measured at baseline and at the end of study using ELISA. The results showed a significant elevation of serum adiponectin concentrations in the curcumin group (mean change 28.9 ± 30.5) in comparison to both curcumin-phospholipid complex (mean change 4.1 ± 15.4) and placebo (mean change −3.5 ± 20.4) groups. Curcumin supplementation increased serum adiponectin concentrations, but this effect was not caused by phospholipid-curcumin complex.

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin

Objective: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability.Methods: In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin.Results: As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague–Dawley rats, the optimized SNEDDS of curcumin–phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS.Conclusion: The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

Antioxidant properties of curcuminoids isolated from Curcuma longa L.

Abstract The evaluation of antioxidant potential of food has received much attention in recent years. Antioxidant compounds can scavenge free radicals and thereby can protect the human body from free radicals. This study was focused on the isolation of curcuminoids from the dried turmeric rhizome, and studying their antioxidant activity. The presence of curcuminoids was identified in turmeric sample by Nuclear Magnetic Resonance (NMR) analysis. Since neutral curcumin is known to be poorly soluble, the synthesis of curcumin-cyclodextrin and curcumin-phospholipid complexes was also performed. The antioxidant activity of isolated curcuminoids was assessed by two methods (ABTS and FRAP assay) and their scavenging activities were compared with those of prepared complexes. The ability to reduce ABTS radical cation decreased as follows: quercetin &gt; trolox &gt; curcuminoids &gt; curcumin-cyclodextrin complex &gt; curcumin-phospholipid complex. The reducing potential of tested samples in descending order was quercetin &gt; trolox &gt; curcumin-cyclodextrin complex &gt; curcuminoids &gt; curcumin-phospholipid complex.

Wound Healing Effect of an in Situ Forming Hydrogel Loading Curcumin-Phospholipid Complex.

Wound is one of most commonly clinical diseases. Curcumin is known to improve wound healing but its bioavailability and therapeutic efficiency are very low. Here we firstly report the application of phospholipid complexes to wound healing. A curcumin-phospholipid complex (CPC) was prepared with a solvent-evaporation method. The X-ray diffraction showed that the CPC was amorphous, which was further demonstrated with the electron microscopy. Furthermore, the CPC was loaded into a poloxamer in situ forming hydrogel (ISG). The CPC ISG showed higher erosion rates than the curcumin ISG due to the amorphous structure of CPC, which could lead to increase in curcumin dissolution. The CPC ISG showed higher wound healing effect than the control on the rat skin wound model especially in the early phase. The epidermal recovery was highly improved by the CPC ISG compared to the control. The CPC ISG is a promising formulation as an effective wound healing dressing.

Pharmacokinetics evaluation of curcumin-phospholipid complex

Objective To evaluate the pharmacokinetics of curcumin phospholipid complex(CCPC)in rats following oral administration.Methods Blood samples were collected from the retinal venous plexus of SD rats after oral administration of CCPC or curcumin(CC),and the blood concentration of curcumin was determined by high-performance liquid chromatography(HPLC).Results The solubility and cumulative dissolution of CCPC(0.150g/L and 68.04%,respectively)were higher than those of CC(0.057g/L and 50.68 %,respectively).The pharmacokinetic parameter of CCPC and CC were calculated as follows:Cmax(74.34±5.57)μg/L and(61.64±4.29)μg/L,Tmax(0.17±0)h and(0.25±0)h,AUC0-t(637.38±30.04)μg·h·L-1 and(172.41±31.66)μg·h·L-1,and AUC0-∞(857.80±223.69)μg·h·L-1 and(191.08±43.27)μg·h·L-1,respectively.The intra-day,inter-day precision,and recovery rate met the criteria for content determination.Conclusion Compared with curcumin,CCPC can be absorbed more rapidly and eliminated more slowly.

Curcuminoid-phospholipid complex induces apoptosis in mammary epithelial cells by STAT-3 signaling

Curcumin (from the rhizome of Curcuma longa) is well documented for its medicinal properties in Indian and Chinese systems of medicine where it is widely used for the treatment of several diseases. Epidemiological observations are suggestive that curcumin consumption may reduce the risk of some form of cancers and provide other protective biological effects in humans. These biological properties have been attributed to curcuminoids that have been widely studied for their anti-inflammatory, anti-angiogenic, antioxidant, wound healing and anti-cancer effects. In this study we have investigated on the effect of a curcumin phospholipid complex on mammary epithelial cell viability. HC11 and BME-UV cell lines, validated models to study biology of normal, not tumoral, mammary epithelial cells, were used to analyse these effects. We report that curcumin acts on STAT-3 signal pathway to reduce cell viability and increase apoptosis evaluated by the the amount of activated caspase 3. Further it reduces MAPK and AKT activations. JSI-124, a STAT-3 inhibitor (100 nM) was able to block the negative effect of curcumin on cell viability and caspase 3 activation. Finally the negative effect of cucumin on cell viability has been impaired in STAT-3i HC11, where STAT-3 protein was greatly reduced by shRNA-interference. These results indicate that curcumin presents a potential adverse effect to normal mammary epithelial cells and that it has a specific effect on signal trasduction in mammary epithelium.

Bioavailability of Curcumin: Problems and Promises

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

Curcumin–phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats

A novel formulation of curcumin in combination with the phospholipids was developed to overcome the limitation of absorption and to investigate the protective effect of curcumin–phospholipid complex on carbon tetrachloride induced acute liver damage in rats. The antioxidant activity of curcumin–phospholipid complex (equivalent of curcumin 100 and 200 mg/kg body weight) and free curcumin (100 and 200 mg/kg body weight) was evaluated by measuring various enzymes in oxidative stress condition. Curcumin–phospholipid complex significantly protected the liver by restoring the enzyme levels of liver glutathione system and that of superoxide dismutase, catalase and thiobarbituric acid reactive substances with respect to carbon tetrachloride treated group ( P < 0.05 and <0.01). The complex provided better protection to rat liver than free curcumin at same doses. Serum concentration of curcumin obtained from the complex (equivalent to 1.0 g/kg of curcumin) was higher ( C max 1.2 μg/ml) than pure curcumin (1.0 g/kg) ( C max 0.5 μg/ml) and the complex maintained effective concentration of curcumin for a longer period of time in rat serum. The result proved that curcumin–phospholipid complex has better hepatoprotective activity, owe to its superior antioxidant property, than free curcumin at the same dose level.