Absorption Of Curcumin Research Articles

Fabrication of a Soybean Bowman-Birk Inhibitor (BBI) Nanodelivery Carrier To Improve Bioavailability of Curcumin.

Curcumin is a poorly water-soluble drug, and its oral bioavailability is very low. Here, a novel self-assembly nanoparticle delivery carrier has been successfully developed by using soybean Bowman-Birk inhibitor (BBI) to improve the solubility, bioaccessibility, and oral absorption of curcumin. BBI is a unique protein, which can be resistant to the pH range and proteolytic enzymes in the gastrointestinal tract (GIT), bioavailable, and not allergenic. The encapsulation efficiencies (EE) and the loading capacities (LC) of curcumin in the curcumin-loaded BBI nanoparticles (Cur-BBI-NPs, size = 90.09 nm, PDI = 0.103) were 86.17 and 10.31%, respectively. The in vitro bioaccessibility of Cur-BBI-NPs was superior to that of curcumin-loaded sodium caseinate (SC) nanoparticles (Cur-SC-NPs) (as control). Moreover, Cur-BBI-NPs significantly enhanced the bioavailability of curcumin in rats compared with Cur-SC-NPs, and the clathrin-mediated endocytosis pathway probably contributed to the favorable bioavailability of Cur-BBI-NPs, as revealed by the cellular uptake inhibition study.

Formulation and Evaluation of Mucoadhesive Buccal Tablets of Curcumin and its Bioavailability Study

Aim: The main objective of the present work is to improve the bioavailability of curcumin by buccal route and to study in-vitro and in-vivo drug release. Materials and Methods: The mucoadhesive buccal tablets were formulated by direct compression method using hydrophilic polymers such as guar gum, xanthan gum, HPMC E15 in different concentration and piperine as permeation enhancers (1%). Ethylcellulose is used as backing layer to promote the unidirectional flow of drug in the buccal region. Curcumin has a number of beneficial activities, such as potent antioxidant, anti-inflammatory, anticancer, anti-rheumatic and anti-diabetic. When Curcumin is administered orally it has low bioavailability because of poor absorption, rapid GIT metabolism and hepatic first pass metabolism. Curcumin has poor aqueous solubility and better lipid solubility, and buccal region consist of lipid, so the absorption of curcumin can be increased by this route. Results and Discussion: The FT-IR spectra of pure drug with different polymers showed no shift in peak, indicating absence of interaction. The prepared formulations were evaluated for pre-compression studies such as bulk density, tapped density, angle of repose. The post-compressions studies such as weight variation, thickness, friability, hardness, mucoadhesive strength, drug content, swelling studies, in-vitro diffusion studies and in-vitro dissolution studies. Conclusion: All the prepared formulations were within the standard Pharmacopoeial limit. The formulation (FX2) containing xanthan gum showed the best dissolution (97.75%) within 4.0 hours and it follows higuchi model. The in-vivo animal study showed the better bioavailability by buccal route when compare to oral route.

Improvement of the Solubility and Intestinal Absorption of Curcumin by N-Acyl Taurates and Elucidation of the Absorption-Enhancing Mechanisms.

In this study, the effects of N-acyl taurates (NATs) on the intestinal absorption of curcumin (CUR), a water-insoluble and poorly absorbed compound, were examined in rats. Sodium methyl lauroyl taurate (LMT) and sodium methyl cocoyl taurate (CMT) were the most effective in increasing the solubility and intestinal absorption of CUR. The intestinal membrane toxicity of the NATs was also evaluated by measuring the activity of lactate dehydrogenase (LDH), a toxicity marker. NATs did not increase the activity of LDH, suggesting that they may be safely administered orally. We further elucidated the absorption-enhancing mechanisms of NATs by using Caco-2 cells. In cellular transport studies, LMT and CMT reduced the transepithelial electrical resistance value of Caco-2 cells and increased the transport of 5(6)-carboxyfluorescein and CUR. Hence, the intestinal absorption enhancement by LMT and CMT was attributed to the synergistic effect of higher solubility and greater permeability of the cell layer towards CUR in the presence of the surfactants. In summary, co-administration of CUR with either LMT or CMT is a simple and effective method to enhance oral delivery of CUR.

Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis

Context: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis. Objective: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis. Materials and methods: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters. Results: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1β and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP. Discussion and conclusion: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.

A Novel Self-Microemulsifying System for the Simultaneous Delivery and Enhanced Oral Absorption of Curcumin and Resveratrol.

The use of curcumin and resveratrol in combination has now become increasingly of interest because of their synergistic effects as therapeutic agents for various diseases, especially cancer. To overcome the poor oral bioavailability of both compounds and improve patient compliance, a novel self-microemulsifying formulation containing curcumin together with resveratrol was developed. Capryol 90, Cremophor EL, and Labrasol were selected as the oil, surfactant, and co-surfactant in the formulation, respectively, based on the solubility study of both compounds. More than 70 % and 80 % of curcumin and resveratrol, respectively, were released in 20 min. The formulation formed a fine oil in water microemulsion with droplet sizes in aqueous media of 15-20 nm. In addition, the formulation containing curcumin and resveratrol showed greater antioxidant activity than that of the formulations with individual compounds, while the cytotoxic activity against HT-29 of the co-formulation (IC50 = 18.25 µM; curcumin and resveratrol in the ratio 1 : 1) was less than the formulation with only curcumin (IC50 = 30.1 µM) and only resveratrol (IC50 = 25.4 µM). After oral administration to rabbits, the self-microemulsifying formulation containing curcumin together with resveratrol increased the total plasma concentrations of curcumin and resveratrol by 10-fold and 6-fold, respectively, compared to the unformulated combination. This study clearly demonstrated the potential use of the self-microemulsifying formulation for co-delivery, and enhanced oral absorption of poorly water-soluble natural compounds. In addition, the combination was found to produce synergistic antioxidant activity and cytotoxicity against HT-29 cells.

Combined therapy using bevacizumab and turmeric ethanolic extract (with absorbable curcumin) exhibited beneficial efficacy in colon cancer mice

Turmeric is commonly used as a medicinal herb and dietary supplement. Its active ingredient, curcumin, has been shown to possess antitumor effects in colorectal cancer patients. However, poor absorption of curcumin in intestine impedes its wide clinical application. Our previous findings showed that the presence of turmerones increased the accumulation of curcumin inside colonic cells. Hence, we hypothesized that curcumin with turmerones or present in turmeric ethanolic extract would augment its anti-tumor activities in tumor-bearing mice. The pharmacokinetics of curcumin in different preparations (containing same amount of curcumin) were studied in mice. The anti-tumor efficacies of curcumin or turmeric extract (with absorbable curcumin) in combination with bevacizumab were further investigated in HT29 colon tumor-bearing mice. Pharmacokinetic results showed that the plasma curcumin level of turmeric extract-fed mice was the highest, suggesting turmeric extract had the best bioavailability of curcumin. Besides, combined turmeric extract plus bevacizumab treatment significantly inhibited the tumor growth. Such inhibitory effects were stronger than those of curcumin plus bevacizumab or bevacizumab alone and were comparable with those of 5-fluorouracil+leucovorin+oxaliplatin (FOLFOX) plus bevacizumab. Notably, there was no observable side effect induced by turmeric extract treatment while significant side effects were found in FOLFOX-treated mice. In conclusion, combination of turmeric extract with bevacizumab possessed potent anti-tumor effects without observable side effects, strongly suggesting the adjuvant use of turmeric extract in colorectal cancer therapy. Our current findings warrant the confirmation regarding the benefits arising from the combined use of bevacizumab and turmeric in colorectal cancer patients in the near future.

BSA-dextran emulsion for protection and oral delivery of curcumin

In this study, BSA-dextran conjugate, produced by Maillard reaction, was used as emulsifier and stabilizer to produce curcumin-loaded oil in water emulsions. At fixed pH and BSA-dextran concentration in aqueous phase, the increases of curcumin concentration in oil phase from 12 to 15 mg/mL and oil volume fraction from 20% to 40% did not influence curcumin loading efficiency, but the oil-water interfacial films became imperfect, which were observed by transmission electron microscopy. The emulsion with integrated and cross-linked interfacial film formed on a heat treatment was long-term stable at various temperature and pH conditions, including physical stability of the emulsion and chemical stability of the loaded curcumin. Ex vivo fluorescence images of mice by means of hydrophobic fluorescence probe-loaded BSA-dextran emulsion revealed that the emulsion and/or released probe were mainly in gastrointestinal tract after oral administration and almost disappeared at 24 h post-administration. The pharmacokinetics analysis demonstrated that curcumin-loaded BSA-dextran emulsion could increase curcumin oral bioavailability in mice by 4.8-fold compared with curcumin/Tween 20 suspension. This study verifies that the emulsion can protect loaded curcumin from decomposition and also can promote curcumin absorption in gastrointestinal tract, indicating that protein-polysaccharide emulsions are good oral delivery systems for hydrophobic drugs and nutrients.

Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption

In order to improve the oral absorption of curcumin, curcumin-loaded lipid cubic liquid crystalline nanoparticles were prepared and evaluated in vitro and in vivo. The hot and high-pressure homogenization method was used to prepare the nanoparticles. The formulation and process were optimized by uniform design with drug loading and entrapment efficiency as index, and physicochemical properties were also investigated. Spherical nanoparticles were observed under transmission electron microscope (TEM), with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 ± 0.2)% and entrapment efficiency of (95 ± 1.8)%. The in vitro release of curcumin from the nanoparticle formulation showed a sustained property, while the pharmacokinetics results after oral administration of curcumin loaded lipid cubic liquid crystalline nanoparticles in rat showed that the oral absorption of curcumin fitted one-compartment model and relative bioavailability was 395.56% when compared to crude curcumin. It can be concluded from these results that the lipid cubic liquid crystalline nanoparticles, as carriers, can markedly improve the oral absorption of curcumin.

The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo

Curcumin-loaded self-assembled polymeric micelles (Cur-PMs) were designed to increase oral bioavailability of curcumin and investigate the oral absorption mechanism in vitro and in vivo. The Cur-PMs were spherical nano-size particles 17.82±0.33nm in size, with a drug loading of 3.52±0.18%, and encapsulation efficiency as high as 93.08±2.23%. The intestinal absorption of Cur-PMs in the duodenum, jejunum, and ileum was 3.09-, 6.48-, and 1.78-fold greater than that of curcumin solution (Cur-Sol) at 0.5h. The cellular uptake of Cur-PMs in Caco-2 cells was significantly enhanced in comparison with Cur-Sol by caveolae-mediated and clathrin-mediated endocytosis. Moreover, the apparent permeability coefficient (Papp) of Cur-PMs was 3.50-fold higher than that of Cur-Sol in Caco-2 transport studies. The transport mechanism of Cur-PMs into the system circulation was not paracellular transport through opening the tight junctions, but was by energy-dependent, macropinocytic transcytosis and lymphatic transport pathways. Furthermore, the AUC(0−t) value of Cur-PMs was improved 2.87-fold compared with that of Cur-Sol after oral administration in rats. Therefore, self-assembled polymeric micelles could be a promising vehicle to efficiently improve the oral absorption of curcumin.

Influence of particle size on the in vitro and in vivo anti-inflammatory and anti-allergic activities of a curcumin lipid nanoemulsion.

The polyphenolic compound, curcumin, is a natural yellow pigment component of turmeric. It exerts various biological effects, such as anti-inflammatory effects, and we have previously demonstrated that curcumin is a specific inhibitor of DNA polymerase λ. Curcumin is characterized by poor bioavailability as it is water-insoluble, is poorly absorbed and is systemically eliminated. In order to increase the bioavailability of curcumin, in this study, we produced a curcumin-loaded lipid nanoemulsion of various particle sizes (50, 100 and 200 nm). The curcumin lipid nanoemulsion was prepared by a modified thin-film hydration method followed by sonication. To identify the optimal particle size which exhibits the strongest physiological activity, we investigated the inhibitory effects of the obtained nanoemulsions against inflammatory and allergic activities. In in vitro cell culture experiments, the 100-nm curcumin lipid nanoemulsion showed the most prominent inhibitory effect on the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW264.7 murine macrophages, and on the release of β-hexosaminidase induced by the calcium ionophore, A23187, in rat basophilic leukemia RBL-2H3 cells. In an in vivo experiment, in which mice were administered the curcumin-loaded lipid nanoemulsion of various particle sizes, the 100-nm curcumin lipid nanoemulsion showed the most prominent anti-inflammatory and anti-allergic effects, inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema and immunoglobulin E (IgE)-induced passive cutaneous anaphylactic (PCA) reaction. The effects of particle size on serum curcumin absorption were also assessed in mice, and the 100-nm lipid nanoemulsion showed the greatest absorption. The results from our study suggest that the physiological activities of curcumin lipid nanoemulsions differ depending on particle size. Our data indicate that the curcumin lipid nanoemulsion with a particle size of 100 nm has potential for use in enhancing the bioavailability and medical value of curcumin.

Self-microemulsifying drug delivery system of curcumin with enhanced solubility and bioavailability using a new semi-synthetic bicephalous heterolipid: in vitro and in vivo evaluation

Curcumin SMEDDS from heterolipid E1E.

Microencapsulation of Turmeric Oleoresin by Spray Drying and In Vitro Release Studies of Microcapsules

AbstractThe present work reports on the microencapsulation of turmeric oleoresin by spray drying using different ratios of maltodextrin and gum arabic (100:0–0:100) as wall material. Solvent‐extracted and commercial oleoresin microcapsules prepared using gum arabic alone as wall material and spray dried at the inlet air temperature of 175C showed higher encapsulation efficiency of 71.74 and 73.67%, maximum curcumin of 3.41 and 3.39 g/100 g and oleoresin content of 7.16 and 7.29 g/100 g, respectively. Stability of microcapsules against light, oxygen and heat was higher than the nonencapsulated oleoresin. In vitro release study showed initial burst release followed by a controlled release of curcumin from microcapsules over a period of 1 week.Practical ApplicationsTurmeric oleoresin is an approved natural colorant that is prepared by solvent extraction of turmeric powder. It is a mixture of curcumin, volatile oil, nonvolatile fatty and resinous material, and other active ingredients. Curcumin has a number of potentially beneficial biological activities such as antitumor, antioxidant, antimicrobial and anti‐inflammatory properties. But it is readily decomposed when exposed to bright light, high temperature or oxidative conditions. Microencapsulation of turmeric oleoresin protects it against destructive changes, converts it into a free‐flowing powder and controls the release of curcumin. Because the prepared turmeric oleoresin microcapsules are in the powder form, it can be used easily as a natural colorant in foods. Also oleoresin microcapsule provides longtime retention of curcumin in the stomach, thus helping in better and complete absorption of curcumin. Hence, these microcapsules can be used as a therapeutic agent.

Validation of photodynamic action via photobleaching of a new curcumin-based composite with enhanced water solubility.

Motivated by the photochemical and photophysical properties of curcumin-based composites, the characteristics of a new curcumin-based water-soluble salt were investigated via absorption and fluorescence spectroscopy. Photobleaching was investigated using a set of LEDs in three different wavelengths (405nm, 450nm and 470nm) to illuminate an aqueous solution of curcumin, evaluating its degradation for five different exposure times (0, 5, 15, 45 and 105minutes). The results were compared with equivalent measurements of dark degradation and illumination in the presence of a singlet-oxygen quencher. Three solution concentrations (50, 100 and 150μg/ml) were studied. To measure the fluorescence, it was used low power 405nm excitation laser source. Time dependent photodegradation of curcumin was observed, as compared to the natural degradation of samples maintained on a dark environment. Two main absorption peaks were detected and their relation responded to both concentration and wavelength of the illumination source. A spectral correlation between absorption of curcumin and the emission bands of the sources showed an optimal spectral overlap for the 450nm LED. For this source, photobleaching showed a less intense degradation on the presence of singlet oxygen quencher. This last result confirmed singlet oxygen production in vitro, indicating a strong potential of this composite to be used as a blue-light-activated photosensitizer.

Optimization, characterization and in vitro evaluation of curcumin microemulsions

The purpose of this study was to improve the solubility and the stability and oral uptake of curcumin by developing an o/w microemulsion, using food grade components. Three microemulsions were developed and characterized, stabilized by non ionic surfactants Cremophor EL, Tween 20, Tween 80 or Lecitin and containing a variety of oils, namely olive oil, wheat germ oil, vitamin E. Chemical and physical stabilities of three systems was also evaluated within two months. The oral absorption of curcumin from the best microemulsion was investigated in vitro using parallel artificial membrane permeability assay (PAMPA). The optimal formulation consisted of 3.3 g/100 g of vitamin E, 53.8 g/100 g of Tween 20, 6.6 g/100 g of ethanol and water (36.3 g/100 g), with a maximum solubility of curcumin up to 14.57 mg/ml and a percentage of permeation through the artificial membrane of about 70%.

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin

Purpose: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.Methods: The formulation was optimized by Plackett–Burman screening design and Box–Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.Results: The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of −24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t1/2 of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution.Conclusion: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes

Curcumin revealed various health-beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences. In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration-time curve (AUC), the micronized curcumin was 14-, 5-, and 9-fold and micellar curcumin 277-, 114-, and 185-fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.

Effect of nanostructured lipid vehicles on percutaneous absorption of curcumin

The present study describes the production and characterization of monoolein aqueous dispersions (MAD) and lecithin organogels (ORG) as percutaneous delivery systems for curcumin (CUR).In particular, MAD stabilized by sodium cholate/poloxamer and w0 3 ORG lipid carriers, both in the presence and absence of CUR, have been considered: MAD morphology and dimensional distribution have been investigated by Cryogenic Transmission Electron Microscopy (cryo-TEM) and Photon Correlation Spectroscopy (PCS), while the inner structure of MAD and ORG has been studied by X-ray scattering techniques. As a general result, CUR chemical stability has been found to be better controlled by MAD, probably because CUR is more protected in the case of CUR-MAD with respect to CUR-ORG.To investigate the performance of differently composed lipid formulations as CUR delivery system, in vitro studies, based on Franz cell and stratum corneum–epidermis (SCE) membranes, and in vivo studies, based on skin reflectance spectrophotometry and tape stripping, were then performed. The results indicated that ORG induces a rapid and intense initial penetration of CUR probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum. Conversely, CUR incorporated into MAD can be released in a controlled fashion possibly because of the formation of a CUR depot in the stratum corneum. In this respect ORG could be employed in pathologies requiring rapid CUR action, while MAD could be proposed for assuring a prolonged CUR activity.

Intranasal curcumin and its evaluation in murine model of asthma

Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect.

Development and evaluation of a novel phytosome-loaded chitosan microsphere system for curcumin delivery

In this study, we developed a novel drug delivery system, curcumin-phytosome-loaded chitosan microspheres (Cur-PS-CMs) by combining polymer- and lipid-based delivery systems. Curcumin exhibits poor water-solubility and is rapidly eliminated from the body. We aimed to use our novel delivery system to improve the bioavailability and prolong the retention time of curcumin in the body. The Cur-PS-CMs were produced by encapsulating curcumin-phytosomes (Cur-PSs) in chitosan microspheres using ionotropic gelation. The final microsphere was spherical, with a mean particle size of 23.21 ± 6.72 μm and drug loading efficiency of 2.67 ± 0.23%. Differential scanning calorimetry and Fourier transform infrared spectroscopy demonstrated that the integrity of the phytosomes was preserved within the polymeric matrix of the microspheres. The in vitro release rate of curcumin from the Cur-PS-CMs was slower than that from curcumin-loaded chitosan microspheres (Cur-CMs) in pH 1.0, 4.0, 6.8, and 7.4. Pharmacokinetic studies in rats dosed with Cur-PS-CMs showed a 1.67- and a 1.07-fold increase in absorption of curcumin compared with Cur-PSs and Cur-CMs, respectively. The half-life of curcumin orally administration of Cur-PS-CMs (3.16 h) was longer than those of Cur-PSs (1.73 h) and Cur-CMs (2.34h). These results indicated that the new Cur-PS-CMs system combined the advantages of chitosan microspheres and phytosomes, which had better effects of promoting oral absorption and prolonging retention time of curcumin than single Cur-PSs or Cur-CMs. Therefore, the PS-CMs may be used as a sustained delivery system for lipophilic compounds with poor water-solubility and low oral bioavailability.

Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability

Curcumin, a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of Curcumin in inflammatory disorders, cardiovascular disease, cancer, Alzheimer’s disease and neurological disorders have been shown. However, the clinical application of Curcumin is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based drug delivery systems for Curcumin including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanoemulsions, complexes and dendrimer/dimer, have been attempted to enhance the oral bioavailability, biological activity or tissue-targeting ability of Curcumin. We attempted the nanosuspensions based delivery of curcumin. Nanonisation renders curcumin completely dispersible in aqueous media. To enhance the curcumin absorption by oral administration, nanoparticulate solid oral formulation of curcumin was prepared by us and the resulting capsule was then examined for its efficiency on bioavailability in Male Wistar rats at a dose of 100 mg curcumin/kg body weight and the pharmacokinetic parameters were compared to those of normal curcumin powder and a commercial curcumin capsule CUR-500. The bio-distribution of curcumin in organs of rat was also studied. Nanoparticulation significantly raised the curcumin concentration in selective organs in the body. The results obtained provide promising results for nanoparticulate Curcumin to improve its biological activities. Enhanced bioavailability of curcumin in the form of nanoparticle is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease. The available information also strongly suggests that nano-formulation of ingredients such as curcumin may be used as a novel nutrient delivery system too.