Water Solubility Of Curcumin Research Articles

HSA-curcumin nanoparticles: a promising substitution for Curcumin as a Cancer chemoprevention and therapy.

Many solutions have been evaluated to deal with "chemotherapy and radiation-resistant cancer cells' as well as "severe complications of chemotherapy drugs". One of these solutions is the use of herbal compounds with antioxidant properties. Among these antioxidant compounds, curcumin is identified as the strongest one to inhibit cancerous cells proliferation. However, its clinical trials have encountered many constraints, because curcumin is insoluble in water and unstable in physiological conditions. To overcome these limitations, in this study, curcumin was conjugated with human serum albumin (HSA) and its effects on breast cancer cell lines were also measured. After making of HSA-curcumin nanoparticles (NPs) by the desolvation technique, they were characterized by the FTIR, DLS, TEM, and SEM method. At the end, its anticancer effects have been examined using MTT test and apoptosis assay. The FTIR graph confirmed that curcumin and HSA have been conjugated along with each other. Particles size was reported to be 220nm and 180nm by DLS and SEM, respectively. The zeta potential of HSA-curcumin NPs was -7mV, while it was -37mV for curcumin. The MTT and apoptosis assay results indicated that the toxicity of HSA-curcumin NPs on the normal cell are less than curcumin; however, its anti-cancer effects on the cancer cells are much greater, compared to curcumin. HSA-curcumin NPs increase curcumin solubility in water as well as its stability in physiological and acidic conditions. These factors have the ability of overwhelming the limitations on using curcumin alone, and they could result in a significant increase in the toxicity of curcumin on the cancer cells without increasing its toxicity on the normal cells. Grapical abstract.

Fabrication of curcumin-loaded zein nanoparticles stabilized by sodium caseinate/sodium alginate: Curcumin solubility, thermal properties, rheology, and stability

Curcumin is a polyphenol with multiple biological activities, but its extremely poor water solubility severely limits its application in the food industry. The purposes of this work were to study the effect of nano-encapsulation on the water solubility of curcumin (C), the interaction of curcumin with zein (Z), the thermal properties, rheological properties, and the stability under different environmental pressures of the nanoparticles. The results of particle size, zeta potential, and surface hydrophobicity (H0) indicated that the combination of coating materials including sodium caseinate (SC) and sodium alginate (SA) with zein nanoparticles by electrostatic interaction led to a gradual increase in the particle size of composite nanoparticles and a decrease in surface hydrophobicity. The nano-encapsulation significantly improved the water solubility of curcumin and causing its crystal structure to change to an amorphous state. Fourier transform infrared spectroscopy confirmed that curcumin bound to zein through hydrogen bonding. Rheological test results showed that the coating materials combined with zein led to an increase in the apparent viscosity of the nanoparticles. The stability analysis results indicated that the composite nanoparticles with a sodium alginate coating have excellent stability of pH, salt solution and storage, and excellent anti-gastrointestinal fluids digestion characteristics when compared to pure protein nanoparticles.

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions

Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, co-surfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin.

Spectroscopic studies on the molecular interactions of curcumin and piperine

The diarylheptanoid curcumin is the yellow coloring agent accumulated in the rhizome of the common spice turmeric (Curcuma longa L.). It has gathered a lot of pharmaceutical interest over the last decades due to some positive effects on human health. However, the use of curcumin as a drug is prevented by its low bioavailability and solubility in water. Interestingly, piperine, the pungent constituent of household pepper (Piper nigrum L.) is able to increase the bioavailability of curcumin up to 20-fold without any known adverse effects. The mechanism responsible for this piperine-based increase of curcumin bioavailability is, however, not fully understood. In a recent publication, a quantum chemical study suggested the formation of a molecular complex between curcumin and piperine being responsible for this effect. The present work now revealed that indeed a 1:1 complex formation can be observed in NMR titration experiments and by mass spectrometry, but the complex strength is rather low (K ~ 1.5 dm3/mol). Furthermore, it is shown that the presence of piperine does not increase the water solubility of curcumin, which makes it rather improbable that such a complex is the main reason for an enhanced curcumin bioavailability.Graphic abstract

Fast-dissolving antioxidant curcumin/cyclodextrin inclusion complex electrospun nanofibrous webs

Curcumin/Hydroxypropyl-beta-Cyclodextrin (HP-β-CyD) and Curcumin/Hydroxypropyl-gamma-Cyclodextrin (HP-γ-CyD) inclusion complex nanofibrous webs were produced using electrospinning technique for the purpose of orally fast-dissolving antioxidant food supplement. Curcumin was totally preserved without any loss during the electrospinning process. The aqueous solutions of curcumin/HP-β-CyD and curcumin/HP-γ-CyD were yielded uniform fiber morphology with ~200 nm and ~900 nm average fiber diameter, respectively. Both Curcumin/CyD webs were produced in the form of free-standing and flexible character. Curcumin is a natural bioactive compound with poor water-solubility, however, the phase solubility test and dissolution/disintegration tests (water and artificial saliva) revealed that the water-solubility of curcumin was prominently improved by inclusion complexation with CyD. The antioxidant effect of curcumin in Curcumin/CyD webs was also enhanced due to higher solubility of curcumin by CyD inclusion complex. The results showed that HP-γ-CyD is significantly more effective than HP-β-CyD in order to enhance the solubility and antioxidant property of curcumin in Curcumin/CyD webs.

Small molecule induced toxic human-IAPP species characterized by NMR.

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed. CurDAc interaction with amyloid is structurally selective, which is reflected in a strong interference with hIAPP aggregation while showing weaker interactions with human-calcitonin and amyloid-β1-40 in comparison. Remarkably, CurDAc also exhibited potent fiber disaggregation for hIAPP generating a toxic oligomeric species.

Photodynamic inactivation of S. aureus with a water-soluble curcumin salt and an application to cheese decontamination.

In this study, the optimal parameters for the photodynamic inactivation (PDI) of Staphylococcus aureus in bacterial suspensions and in cheese were assessed using a water-soluble curcumin salt as the photosensitizer (PS). The in vitro study aimed at finding the optimal concentration and light dose to promote S. aureus photokilling. Four main groups were proposed: CONTROL (L-C-), LIGHT (L+C-), CUR (L-C+) and PDI (L+C+). A fixed light dose (LED, 450 ± 10 nm, 10 J cm-2) was applied using four different PS concentrations (0.75, 1.0, 1.5 and 3.0 mg mL-1). The dose also varied from 10-100 J cm-2 for a fixed concentration. High inactivation rates were observed for all light doses, with a maximum reduction of 7.58 log10 at 100 J cm-2 (p ≪ 0.05). Saturation of the PDI effect was observed after a 10 minute illumination time, as well as a slight decrease in the S. aureus population for increasing illumination times in the L+C- group. As an application, the concentration showing the best decontamination performance in vitro (0.75 mg mL-1) was applied to decontaminate cheese in loco. PDI in two types of coalho cheese, a rennet-coagulated cheese commonly consumed in Brazil, was investigated. The results showed no significant inactivation in unpasteurized cheese, but a 4.34 log10 reduction for t > 5 min in pasteurized specimens. In conclusion, the present PDI-catalyzed curcumin photosensitizer inactivated S. aureus at statistically significant levels in vitro, in pasteurized cheese, but not in unpasteurized specimens.

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.

Synthesis and characterization of stevioside having low degree polymerized glucosides using dextransucrase and dextranase

Transglycosylation is one of enzymatic methods to improve the physical and biochemical properties of various functional compounds. In this study, stevioside glucosides were synthesized using sucrose as a substrate, stevioside (Ste) as an acceptor, and dextransucrase from Leuconostoc mesenteroides B-512 F/KM. The highest Ste conversion yield of 98% was obtained with 50 mg/mL Ste, 800 mM sucrose, and dextransucrase 4 U/mL at 28 °C for 6 h. The concentration of Ste was unchanged while of Ste-G1 was increased from 7.7 mM to 9.1 mM as the Ste acceptor reaction digest was treated with dextranase from Lipomyces starkeyi. Ste-G1 (13-O-β-sophorosyl-19-O-β-isomaltosyl-steviol), Ste-G2 (13-O-(β-(1→6) glucosyl)-β-glucosylsophorosyl-19-O-β-isomaltosyl-steviol), and Ste-G2′ (13-O-β-sophorosyl-19-O-β-isomaltotriosyl-steviol) were determined by NMR. These glucosylated Ste showed increased stabilities at pH 2, 60 °C for 48 h as compared to Ste. Ste-G1, Ste-G2, and Ste-G2′ inhibited the insoluble glucan synthesis from sucrose by mutansucrase from Streptococcus muntans by the transfer of the glucosyl group of sucrose to Ste-G1, Ste-G2, and Ste-G2′. The relative water solubility of curcumin, pterostilbene or idebenone was increased by Ste or Ste glucosides treatment. Ste and Ste-G1 restored cell viability in RAW264.7 cells at concentrations up to 8 mg/mL and inhibited nitric oxide production in LPS-induced RAW264.7 cells with IC50 of 3.29 and 1.87 mg/mL.

Robust Microfluidic Technology and New Lipid Composition for Fabrication of Curcumin-Loaded Liposomes: Effect on the Anticancer Activity and Safety of Cisplatin.

Curcumin exhibits potent anticancer activity via various mechanisms, but its in vivo efficacy has been hampered by poor solubility. Nanotechnology has been employed to deliver curcumin, but most of the reported systems suffered from low drug loading capacity and poor stability. Here, we report the development and optimization of a liposomal formulation for curcumin (Lipo-Cur) using an automated microfluidic technology. Lipo-Cur exhibited a mean diameter of 120 nm with a low polydispersity index (<0.2) and superior loading capacity (17 wt %) compared to other reported liposomal systems. Lipo-Cur increased the water solubility of curcumin by 700-fold, leading to 8-20-fold increased systemic exposure compared to the standard curcumin suspension formulation. When coadministered with cisplatin to tumor-bearing mice, Lipo-Cur augmented the antitumor efficacy of cisplatin in multiple mouse tumor models and decreased the nephrotoxicity. This is the first report demonstrating the dual effects of curcumin enabled by a nanoformulation in enhancing the efficacy and reducing the toxicity of a chemo-drug in animal models under a single and low dose administration.

PH‐Sensitive Poly(ethylene glycol)/Poly(ethoxyethyl glycidyl ether) Block Copolymers: Synthesis, Characterization, Encapsulation, and Delivery of a Hydrophobic Drug

AbstractCurcumin is a natural polyphenolic compound known for its numerous pharmacological properties. However, its low water solubility and instability at neutral pH are serious drawbacks preventing its use as an oral drug. Well‐defined amphiphilic poly(ethylene glycol)‐block‐poly(ethoxyethyl glycidyl ether) (PEG‐b‐PEEGE) block copolymers carrying acid‐labile acetal groups are synthesized by anionic ring‐opening polymerization and investigated as potential pH‐sensitive nano‐carriers for delivery of curcumin to cancer cells. The nanoparticles, resulting from copolymer self‐assembly in aqueous media, are characterized by dynamic light scattering and cryo‐transmission electron microscopy. The nanoparticles’ stabilities are evaluated in three different phosphate buffers (pH = 7.2, 6.4, and 5.3). The stability decreases at lower pH and a complete disappearance of the nanoparticles is noticed after 4 days at pH 5.3. Curcumin is encapsulated in hydrophobic core of mPEG40‐b‐PEEGE25 nanoparticles allowing significant enhancements of curcumin solubility in water and lifetime at neutral pH. In vitro curcumin release is studied at different pH by UV‐spectroscopy and high‐performance liquid chromatography (HPLC). The cytotoxicity of curcumin and curcumin encapsulated in micelles is evaluated by cell viability 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay on MDA‐MB‐231 human breast cancer cells.

Investigation of Curcumin Water Solubility Through Emulsifying with Biocompatible Polyethylene Glycol–Based Polymers

The low water solubility of curcumin prevents various biological and pharmacological activities, which prevent adequate bioavailability. Herein, two new emulsifier systems have been developed and optimized to increase the water solubility of curcumin. The first emulsion system containing curcumin was prepared using polyethylene glycol monooleate-460 (PEG-oleate) for the oily phase, Tween 20 as the emulsifier, and acetic acid as stabilizing agent. In this emulsion system, Box–Behnken experiment design was applied to find the most favorable conditions and substance ratios. Transmission electron microscopy (TEM) analysis was performed for the emulsion system obtained under optimum conditions. For this emulsion system, the curcumin solubility was found to be 709 times higher than the solubility of raw curcumin. The second emulsion systems developed was carried out using our newly synthesized methoxy polyethylene glycol monooleate-550 (methoxy PEG-oleate). The best curcumin solubility was obtained when the ratio of curcumin-methoxy PEG-oleate was 1:5 (w/w). The solubility of curcumin in this system was 56 times higher than that of raw curcumin. Interactions were characterized by FTIR measurements. Solubility, encapsulation capacity, dissolution, and stability studies were performed. The amount of curcumin in the emulsion systems was carried out by newly developed reversed phase high-performance liquid chromatography.

Production and characterisation of bacterial cellulose hydrogels loaded with curcumin encapsulated in cyclodextrins as wound dressings

Natural bioactive materials with wound healing properties such as curcumin are attracting interest due to the emergence of resistant bacterial strains. The hydrophobicity of curcumin has been counteracted by using solubility enhancing cyclodextrins. Hydrogels facilitate wound healing due to unique properties and 3D network structures which allows encapsulation of healing agents. In this study, biosynthetic cellulose produced by Gluconacetobacter xylinus (ATCC 23770) was loaded with water soluble curcumin:hydroxypropyl-β-cyclodextrin supramolecular inclusion complex produced by a solvent evaporation method to synthesise hydrogel dressings. The ratios of solvents to solubilise curcumin and hydroxypropyl-β-cyclodextrin were tested for the production of the inclusion complex with optimum encapsulation efficacy. The results confirmed that hydroxypropyl-β-cyclodextrin enhanced the aqueous solubility of curcumin and allowed loading into bacterial cellulose hydrogels. These hydrogels were characterised for wound management applications and exhibited haemocompatability, cytocompatability, anti-staphylococcal and antioxidant abilities and therefore support the potential use of the curcumin:hydroxypropyl-β-cyclodextrin-loaded-bacterial cellulose as hydrogel dressings.

Hybrid layered double hydroxides-curcumin thin films deposited via Matrix Assisted Pulsed Laser Evaporation-MAPLE with photoluminescence properties

Curcumin (CR) is a natural compound with a well-known antioxidant and therapeutic activity. Its stability may be enhanced when incorporated in different matrices as a layered double hydroxides (LDH) matrix. Curcumin intercalated layered double hydroxide nanohybrid is a potential drug delivery system for effective photodynamic therapy in human breast cancer or skin cancer.The synthesis of the hybrid LDH-CR powder implies the dissolution of CR in water or in another organic solvent which is miscible with water. Since the solubility of curcumin in water is very weak, the aim of this study is to investigate the effect of the solvent employed for its dissolution on the structural and physico-chemical-photoluminescent properties of the resulting hybrid materials. Four powders of curcumin (CR)-containing Mg2.5Al-LDH hybrids (Mg/Al molar ratio of 2.5) were prepared by co-precipitation (P) and reconstruction (R) using two different solvents for the dissolution of curcumin: (i) an alkaline aqueous solution (A), and (ii) ethanol (E). The reconstruction used the calcinated (460 °C for 18 h) form of the parent Mg2.5Al-LDH powder. All the solids were characterized by X-ray diffraction (XRD), and FTIR spectroscopy. The FTIR-ATR spectra of the all the powders except the powder prepared via reconstruction in ethanol exhibit LDH characteristics, consistent with the XRD results.Matrix Assisted Pulsed Laser Evaporation (MAPLE) was employed for the deposition of hybrid LDH-CR thin films. Aqueous solutions of the as prepared hybrid LDH-CR powders were frozen and used as targets for MAPLE depositions. The films were deposited using a nanosecond laser emitting at 266 nm. MAPLE is considered a “soft” deposition technique suitable to conserve the CR stability. XRD, scanning electron microscopy, FT-IR spectroscopy and fluorescence measurements were used to characterize the deposited films in order to evidence the influence of the preparation methods on the structural and photophysical characteristics of the hybrid LDH-CR films.

Synthesis and controlled release of curcumin‐β‐cyclodextrin inclusion complex from nanocomposite poly(N‐isopropylacrylamide/sodium alginate) hydrogels

ABSTRACTInclusion complex of curcumin with β‐cyclodextrin (Cur‐β‐CD) was prepared using coprecipitation method. Stoichiometric ratio between curcumin and β‐cyclodextrin was found to be 1:2 with an association constant of3.80 × 108M−2using Benesi–Hildebrand method. Inclusion complex formation was confirmed by FTIR and DSC analyses. Water solubility of curcumin increased from 0.00122 to 0.721 mg mL−1with the inclusion complex formation. Release of the inclusion complex from the nanocomposite and conventional poly(N‐isopropylacrylamide/sodium alginate hydrogels crosslinked by nanoclay andN,N′‐methylenebis(acrylamide) (BIS), respectively, were investigated in simulated gastrointestinal conditions. Swelling ratio and cumulative release were dependent on the hydrogel composition and pH. At pH = 1.2, hydrogels showed the lowest release ratio, but at pH = 6.8 highest swelling ratios were attained. The swelling ratio and cumulative release decreased with increasing the nanoclay content in nanocomposite hydrogels. On the contrary, as the ratio of BIS in the conventional hydrogels increased, the swelling ratio and cumulative release increased. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47554.

Nghiên cứu phức hợp của curcumin với hydroxypropyl-β-cyclodextrin có sinh khả dụng cao

The biological activity of curcumin in turmeric is of great interest because of its usefulness in food, cosmetics as well as in the treatment of human disease. However, the bioavailability of curcumin has not been fully exploited due to low solubility leading to poor absorption, metabolism and rapid clearance from the body. The study was conducted to improve the bioavailability of curcumin by improving solubility by forming a complex of curcumin with hydroxylpropyl-β-cyclodextrin (HP-β-CD), a substance believed to increase the solubility and stability of the drug. The main chemical constituents of turmeric essential oil and curcuminoid extracted from turmeric powder are ar-turmerone (40.8%) and curcumin (76.4%). The results from the analysis of Fourier-transform infrared spectroscopy (FTIR) showed that curcumin combined with polymers in the complex of curcumin-HP-β-CD and curcumin - HP-β-CD - essential oil. The water solubility of curcumin in the complex of curcumin - HP-β-CD and curcumin - HP-β-CD – essential oil were 159 and 229 times higher than that in raw curcumin, respectively. Mice given the curcumin-HP-β-CD complex had curucmin concentration in the blood about 5 times higher than those given raw curcumin and curcumin - HP-β-CD – essential oil at 8 h after ingestion.

Transdermal delivery of curcumin-loaded supramolecular hydrogels for dermatitis treatment

Curcumin (CUR) is a hydrophobic polyphenol with anti-inflammatory activity. However, its low water-solubility and poor skin permeation limited its application in the treatment of dermititis. CUR-loaded micelles were prepared using thin membrane hydration method with methoxy poly (ethylene glycol)-block-poly (ε-caprolactone) (MPEG-PCL) as carrier material. The drug loading capacity and encapsulation efficiency were 12.14 ± 0.33 and 93.57 ± 1.67%, respectively. CUR-loaded micelles increased CUR's water-solubility to 1.87 mg/mL, being 1.87 × 106-folds higher than native CUR. CUR-loaded supramolecular hydrogels (CUR-H) were prepared through mixing the CUR-loaded micelles solution with α-cyclodextrin (α-CD) solution. The CUR-H presented continuous dissolution behaviour in aqueous medium for 4.5 h. The ex vivo skin permeation test and confocal fluorescence microscopy evaluation confirmed that CUR-H obviously enhanced skin deposition of CUR without drug flux from skin. In vivo experimental results confirmed that the CUR-H was more effective than dexamethasone ointments against croton oil-induced ear edema. The CUR-H composed of MPEG-PCL and α-CD is a promising formulation for skin inflammatory treatment.

CD44 Assists the Topical Anti-Psoriatic Efficacy of Curcumin-Loaded Hyaluronan-Modified Ethosomes: A New Strategy for Clustering Drug in Inflammatory Skin.

Background: Psoriasis is a common chronic inflammatory skin disease. Its treatment is challenged by the limited amount of drug reaching the inflamed skin. The overexpressed CD44 protein in inflamed psoriatic skin can serve as a potential target of novel active-targeting nanocarriers to increase drug accumulation in the skin.Methods: Hyaluronic acid (HA) was linked to propylene glycol-based ethosomes by covalent binding to develop a novel topical drug delivery carrier (HA-ES) for curcumin. An imiquimod-induced psoriasis mouse model was established, and curcumin delivery and anti-psoriatic efficacy using HA-ES were compared with those using plain ethosomes (ES).Results: The HA gel network formed on the surface of HA-ES reduced the leakage and release of poorly water-soluble curcumin. Compared with ES, transdermal curcumin delivery was significantly enhanced by using HA-ES as vehicles; the cumulative transdermal amount and the amount retained in the skin in vitro after 8 h were, respectively, 1.6 and 1.4 times those observed with ES, as well as 3.1 and 3.3 times those observed with a curcumin propylene glycol solution (PGS), respectively. The in vivo psoriatic skin retention of curcumin with HA-ES was 2.3 and 4.0 times that of ES and PGS, respectively. CD44 expression in imiquimod-induced psoriasis-like inflamed skin was 2.7 times that in normal skin. Immunostaining revealed similar results, suggesting that the specific adhesion of HA-ES to CD44 increased drug accumulation in the skin. After topical administration to mice, the HA-ES group showed an alleviation of inflammation symptoms; lower TNF-α, IL-17A, IL-17F, IL-22, and IL-1β mRNA levels; and lower CCR6 protein expression compared to the ES and PGS groups.Conclusion: We demonstrated increased topical drug delivery of curcumin to inflamed tissues using HA-ES targeting the highly expressed CD44 protein. This innovative strategy could be applied for the development of topical drug delivery systems targeting inflamed skin.

Keto-Enol Tautomerism of Temperature and pH Sensitive Hydrated Curcumin Nanoparticles: Their Role as Nanoreactors and Compatibility with Blood Cells.

In order to provide a solution for the poor aqueous solubility and poor bioavailability of curcumin, we present the synthesis and characteristic features of water-soluble curcumin hydrated nanoparticles (CNPs). They are stable and nearly monodisperse in the aqueous phase where the keto form of curcumin self-assembles into spherical CNPs, which are highly sensitive to temperature and pH variations. The CNPs are quite stable up to 40 °C and at neutral pH. A higher temperature range reduces their hydration and makes them unstable, thereby disintegrating them into smaller aggregates. Similarly, a higher pH converts the keto form of CNPs into the enol form by promoting their interparticle fusions driven by hydrogen bonding with a remarkable color change from yellow to bright orange-red which demonstrates their excellent photophysical behavior. The stable keto form CNPs are highly efficient nonreactors for the in situ synthesis of Au, Ag, and Pd NPs which are simultaneously entrapped in curcumin aggregates, thus promoting the metal NP carrying ability of curcumin aggregates. The CNPs also demonstrate their excellent dose-dependent biocompatibility with blood cells. A concentration range up to 5 mM of CNPs is quite safe for their applications in biological systems.

The soluble curcumin derivative NDS27 inhibits superoxide anion production by neutrophils and acts as substrate and reversible inhibitor of myeloperoxidase

A water-soluble curcumin lysinate incorporated into hydroxypropyl-β-cyclodextrin (NDS27) has been developed and shown anti-inflammatory properties but no comparative study has been made in parallel with its parent molecule, curcumin on polymorphonuclear neutrophils (PMNs) and myeloperoxidase (MPO) involved in inflammation. The effect of NDS27, its excipients (hydroxypropyl-β-cyclodextrin and lysine), curcumin lysinate and curcumin were compared on the release of superoxide anion by PMNs using a chemiluminescence assay and on the enzymatic activity of MPO. It was shown that curcumin and NDS27 exhibit similar inhibition activities on superoxide anion release by stimulated PMNs but also on MPO peroxidase and halogenation activities. The action mechanism of curcumin and NDS27 on the MPO activity was refined by stopped-flow and docking analyses. We demonstrate that both curcumin and NDS27 are reversible inhibitors of MPO by acting as excellent electron donors for redox intermediate Compound I (∼107 M−1 s−1) but not for Compound II (∼103 M−1 s−1) in the peroxidase cycle of the enzyme, thereby trapping the enzyme in the Compound II state. Docking calculations show that curcumin is able to enter the enzymatic pocket of MPO and bind to the heme cavity by π-stacking and formation of hydrogen bonds involving substituents from both aromatic rings. Hydroxypropyl-β-cyclodextrin is too bulky to enter MPO channel leading to the binding site suggesting a full release of curcumin from the cyclodextrin thereby allowing its full access to the active site of MPO. In conclusion, the hydroxypropyl-β-cyclodextrin of NDS27 enhances curcumin solubilization without affecting its antioxidant capacity and inhibitory activity on MPO.