Stability of Curcumin Improved in Hydrophobic Based Deep Eutectic Solvents

Turmeric is a commonly known natural spice that contains many phytoconstituents. Among which Curcumin is a polyphenol present in turmeric responsible for many pharmacological actions. Curcumin is still used as a traditional medicine in fields such as Ayurvedic, Siddha, and Unani. Though Curcumin has a large number of activities, it has disadvantages, such as small shelf life due to poor chemical stability, poor absorption results in less bioavailability, less water solubility, rapid metabolism results in quick elimination from the systemic circulation. A Deep eutectic solvent (DES) is a new class of solvents. Hydrophobic DES can be used for dissolving water-insoluble compounds. DES can be prepared when two solid components mixed in a particular proportion are converted into liquid. DES can be used as a solvent for dissolving water-insoluble compounds and to increase the stability. In this work initially, curcumin linearity studies were conducted in different buffers. A buffer showing maximum absorbance was selected from the linearity studies. Then, DES was prepared by combining Camphor:Menthol (1:1) (CM-DES), Camphor:Thymol (1:1) (CT-DES) and, Menthol:Thymol (1:1) (MT-DES). The stability of curcumin in different DES was determined from the stock and working solutions in benchtop condition (room temperature) and, refrigerator condition (5±3°C). Only working solution stability was determined in the in vitro media temperature (37±2°C). From this study, it was concluded that 50 mM Sodium dihydrogen orthophosphate with 0.5% SLS at pH 5.5 showed maximum absorbance value compared with other buffers, so it was selected for further studies. From stability studies, it was found that curcumin in CM-DES was found to be stable in both stock and working solutions compared to the other two CT-DES and MT-DES.

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Toxico-metabolomics study of a deep eutectic solvent comprising choline chloride and urea suggests in vivo toxicity involving oxidative stress and ammonia stress

Green Chemistry ◽

10.1039/d0gc03927f ◽

2021 ◽

Vol 23 (3) ◽

pp. 1300-1311 ◽

Cited By ~ 1

Author(s):

Dasom Jung ◽

Jae Back Jung ◽

Seulgi Kang ◽

Ke Li ◽

Inseon Hwang ◽

...

Keyword(s):

Oxidative Stress ◽

Choline Chloride ◽

Deep Eutectic Solvent ◽

Deep Eutectic Solvents ◽

In Vivo Toxicity ◽

Metabolomics Study ◽

Ammonia Stress

The in vitro and in vivo studies suggest that choline chloride-based deep eutectic solvents may not be considered as pure, safe mixtures even if they consist of safe compounds.

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Resveratrol-Linoleate protects from exacerbated endothelial permeability via a drastic inhibition of the MMP-9 activity

Bioscience Reports ◽

10.1042/bsr20171712 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 2

Author(s):

Aly Shamseddin ◽

Céline Crauste ◽

Erwan Durand ◽

Pierre Villeneuve ◽

Grégor Dubois ◽

...

Keyword(s):

Water Solubility ◽

Critical Role ◽

Deep Eutectic Solvent ◽

Endothelial Permeability ◽

Platelet Endothelial Cell Adhesion ◽

Lipid Derivative ◽

Integrity Protection ◽

Natural Deep Eutectic Solvent

Gelatinolytic matrix metalloproteinases (MMP-2, -9) play a critical role not only in mammals physiology but also during inflammation and healing processes. The natural stilbenoid, resveratrol (RES), exhibits potent antioxidant effects, in a hormetic mode of action, and is known to inhibit MMP-9. However, RES administration exhibits major issues, including poor bioavailability and water solubility, hampering its potential therapeutic effect in vivo. In the present study, we synthesized and evaluated five novel RES–lipid conjugates to increase their cell membrane penetration and improve their bioavailability. The best in vitro MMP-9 inhibitory activity of RES–lipids conjugates was observed with RES-linoleic acid (LA) (5 µM), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCl):water. The inhibition of MMP-9 expression by RES-LA in activated THP-1 monocytes, was, at least due to the deactivation of ERK1/2 and JNK1/2 MAP kinase signaling pathways. Moreover, RES-LA exhibited a strong effect protecting the TNF-α-induced exacerbated permeability in an HUVEC in vitro monolayer (by 81%) via the integrity protection of intercellular junction proteins from the MMP-9 activity. This effect was confirmed by using several complementary approaches including, the real-time monitoring of trans-endothelial electric resistance (TEER), the Transwell HUVEC permeability level, the microscopic examination of the platelet endothelial cell adhesion molecule-1 (CD31/PECAM-1) integrity as well as the fluorescence in intercellular spaces. Consequently, following this strong in vitro proof-of-concept, there is a need to test this promising RES–lipid derivative compound to control the pathological endothelial permeability in vivo.

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Use of Novel Polyurethane Microspheres in a Curcumin Delivery System

Journal of Spectroscopy ◽

10.1155/2014/926268 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Yongmei Hu ◽

Qingshan Li ◽

Wei Hong ◽

Guangzhong Xing ◽

Qilong Jiang ◽

...

Keyword(s):

Water Solubility ◽

Pharmacokinetic Studies ◽

Pharmacological Effects ◽

Ph Variation ◽

Wide Range ◽

Carboxymethyl Cellulose Sodium ◽

The Stability ◽

Scanning Electron

Despite having a wide range of beneficial pharmacological effects, curcumin is characterized by poor water solubility and absorption. In this study, novel polyurethane microspheres containing curcumin (Cur-PUMs) were prepared using carboxymethyl cellulose sodium to improve the bioavailability and prolong the retention time of curcumin. The prepared Cur-PUMs were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, and ultraviolet spectrophotometer. The sustained-release effects of Cur-PUMs were demonstrated using stability testsin vitroandin vivopharmacokinetic studies following oral administration. We found that the stability of Cur-PUMs was strongly affected by pH variation. Further, compared with free curcumin, Cur-PUMs showed significantly improved maximum concentration and half-life.

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Development and Validation of a Discriminating In Vitro Dissolution Method for Oral Formulations Containing Satranidazole

International Journal of Spectroscopy ◽

10.1155/2014/624635 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Harshal Ashok Pawar ◽

Pooja Rasiklal Joshi

Keyword(s):

Water Solubility ◽

Spectroscopic Method ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

Solution Stability ◽

Dissolution Medium ◽

Drug Release Profile ◽

Drug Products ◽

Oral Formulations

The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to the pharmaceutical industry. Satranidazole (BCS Class II drug) is a new nitroimidazole derivative with potent antiamoebic action. There is no official dissolution medium available in the literature. In the present study, parameters such as saturation solubility in different pH medium, dissolution behavior of formulations, influence of sink conditions, stability, and discriminatory effect of dissolution testing were studied for the selection of a proper dissolution medium. Results of solubility data revealed that solubility of Satranidazole decreases with an increase in pH. Satranidazole showed better sink condition in 0.1 N HCl as compared to other media. The drug and marketed formulations were stable in the dissolution media used. An agitation speed of 75 rpm showed a more discriminating drug release profile than 50 rpm. Using optimized dissolution parameters (paddle at 75 rpm, 900 mL 0.1 N HCl) greater than 80% of the label amount is released over 60 minutes. UV-spectroscopic method used was validated for the specificity, linearity, precision, robustness, and solution stability. The method was successfully applied to granular formulations and also to marketed tablets containing 300 mg Satranidazole.

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Performance of Choline Geranate Deep Eutectic Solvent as Transdermal Permeation Enhancer: An In Vitro Skin Histological Study

Pharmaceutics ◽

10.3390/pharmaceutics13040540 ◽

2021 ◽

Vol 13 (4) ◽

pp. 540

Author(s):

Rodrigo Boscariol ◽

Érika A. Caetano ◽

Erica C. Silva ◽

Thais J. Oliveira ◽

Raquel M. Rosa-Castro ◽

...

Keyword(s):

Bioactive Compounds ◽

Research Effort ◽

Histological Study ◽

Research Work ◽

Deep Eutectic Solvent ◽

Skin Barrier ◽

Deep Eutectic Solvents ◽

Transdermal Permeation ◽

Depth Analysis

In the present research work, we addressed the changes in skin by which deep eutectic solvents (DES) enhanced transdermal permeation of bioactive compounds and propose a rationale for this mechanism. Several studies showed that these unusual liquids were ideal solvents for transdermal delivery of biomolecules, but to date, no histological studies relating the action of DES to changes in the structure of the outer skin barrier have been reported. In the research effort described herein, we presented an in-depth analysis of the changes induced in the skin by choline geranate DES, a compound with proven capabilities of enhancing transdermal permeation without deleterious impacts on the cells. The results obtained showed that a low percentage of DES acted as a transient disruptor of the skin structure, facilitating the passage of bioactive compounds dissolved in it.

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Aortic flow below and visceral circulation during aortic counterpulsation: Evaluation of an in vitro model

Perfusion ◽

10.1177/0267659120978641 ◽

2020 ◽

pp. 026765912097864

Author(s):

Monique MJ de Jong ◽

Orlando Parise ◽

Francesco Matteucci ◽

Marcel Rutten ◽

Maxime Devos ◽

...

Keyword(s):

Systemic Circulation ◽

Cardiovascular Model ◽

Mock Circulation ◽

Bland Altman Method ◽

Heart Contraction ◽

Vitro Model ◽

The Stability ◽

Number Of Cycles

Introduction: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance. Methods: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation. Twelve flow probes were placed in the circuit to measure pressures and flows with the IABP on and off. Results: With the balloon off, the meantime to reach the steady state was 48 ± 16 s; with the balloon on, this figure was 178 ± 20 s. The stability of pressure and flow signals was obtained after 72 ± 11 min. The number of cycles of stability of the system was 93 [86–103]. Measurements were reliable either with samples of 10 or 20 beats. Bland Altman method demonstrated the reliability of measurements. Finally, all measurements were comparable to published in vivo data. Conclusion: The presented mock circulation was reliable and gave values with high accuracy both at baseline and during mechanical assistance. This system allows evaluation of the mesenteric flow during IABP, under different clinical/hemodynamic conditions. Nonetheless, its translational potential needs to be further evaluated

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CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.15093 ◽

2016 ◽

Vol 8 (12) ◽

pp. 265 ◽

Cited By ~ 1

Author(s):

Devang Y. Shelat ◽

Sanjeev R Acharya

Keyword(s):

Wistar Rats ◽

Water Solubility ◽

Release Kinetics ◽

Entrapment Efficiency ◽

Systemic Circulation ◽

Oral Route ◽

Male Wistar Rats ◽

Dialysis Bag

Objective: Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.Methods: A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for in vitro release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.Results: A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC50: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for in vitro release profile at different pH with average release obtained between 20-30 min. In vivo kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.Conclusion: The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.

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Silver Nanoparticles and Polyphenol Inclusion Compounds Composites for Phytophthora cinnamomi Mycelial Growth Inhibition

Antibiotics ◽

10.3390/antibiotics7030076 ◽

2018 ◽

Vol 7 (3) ◽

pp. 76 ◽

Cited By ~ 5

Author(s):

Petruta Matei ◽

Jesús Martín-Gil ◽

Beatrice Michaela Iacomi ◽

Eduardo Pérez-Lebeña ◽

María Barrio-Arredondo ◽

...

Keyword(s):

Silver Nanoparticles ◽

Growth Inhibition ◽

Inclusion Compounds ◽

Mycelial Growth ◽

Water Solubility ◽

Phytophthora Cinnamomi ◽

Deep Eutectic Solvent ◽

Phase System ◽

Two Phase

Phytophthora cinnamomi, responsible for “root rot” or “dieback” plant disease, causes a significant amount of economic and environmental impact. In this work, the fungicide action of nanocomposites based on silver nanoparticles and polyphenol inclusion compounds, which feature enhanced bioavailability and water solubility, was assayed for the control of this soil-borne water mold. Inclusion compounds were prepared by an aqueous two-phase system separation method through extraction, either in an hydroalcoholic solution with chitosan oligomers (COS) or in a choline chloride:urea:glycerol deep eutectic solvent (DES). The new inclusion compounds were synthesized from stevioside and various polyphenols (gallic acid, silymarin, ferulic acid and curcumin), in a [6:1] ratio in the COS medium and in a [3:1] ratio in the DES medium, respectively. Their in vitro response against Phytophthora cinnamomi isolate MYC43 (at concentrations of 125, 250 and 500 µg·mL−1) was tested, which found a significant mycelial growth inhibition, particularly high for the composites prepared using DES. Therefore, these nanocomposites hold promise as an alternative to fosetyl-Al and metalaxyl conventional systemic fungicides.

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In Vivo Biocompatible Self-Assembled Nanogel Based on Hyaluronic Acid for Aqueous Solubility and Stability Enhancement of Asiatic Acid

Polymers ◽

10.3390/polym13234071 ◽

2021 ◽

Vol 13 (23) ◽

pp. 4071

Author(s):

Yu Yu Win ◽

Penpimon Charoenkanburkang ◽

Vudhiporn Limprasutr ◽

Ratchanee Rodsiri ◽

Yue Pan ◽

...

Keyword(s):

Hyaluronic Acid ◽

Water Solubility ◽

Aqueous Solubility ◽

Asiatic Acid ◽

Cell Culture Study ◽

Nmr Characterization ◽

The Stability ◽

Stability Enhancement

Asiatic acid (AA), a natural triterpene found in Centalla asiatica, possesses polypharmacological properties that can contribute to the treatment and prophylaxis of various diseases. However, its hydrophobic nature and rapid metabolic rate lead to poor bioavailability. The aim of this research was to develop a thermoresponsive nanogel from hyaluronic acid (HA) for solubility and stability enhancement of AA. Poly(N-isopropylacrylamide) (pNIPAM) was conjugated onto HA using a carbodiimide reaction followed by 1H NMR characterization. pNIPAM-grafted HA (HA-pNIPAM) nanogels were prepared with three concentrations of polymer, 0.1, 0.15 and 0.25% w/v, in water by the sonication method. AA was loaded into the nanogel by the incubation method. Size, morphology, AA loading capacity and encapsulation efficiency (EE) were analyzed. In vitro cytocompatibility was evaluated in fibroblast L-929 cells using the PrestoBlue assay. Single-dose toxicity was studied using rats. HA-pNIPAM nanogels at a 4.88% grafting degree showed reversible thermo-responsive behavior. All nanogel formulations could significantly increase AA water solubility and the stability was higher in nanogels prepared with high polymer concentrations over 180 days. The cell culture study showed that 12.5 µM AA in nanogel formulations was considered non-toxic to the L-929 cells; however, a dose-dependent cytotoxic effect was observed at higher AA-loaded concentrations. In vivo study proved the non-toxic effect of AA loaded in HA-pNIPAM nanogels compared with the control. Taken together, HA-pNIPAM nanogel is a promising biocompatible delivery system both in vitro and in vivo for hydrophobic AA molecules.

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pH, Viscosity of Hydrophobic Based Natural Deep Eutectic Solvents and the Effect of Curcumin Solubility in it

Biointerface Research in Applied Chemistry ◽

10.33263/briac116.1462014633 ◽

2021 ◽

Vol 11 (6) ◽

pp. 14620-14633

Keyword(s):

Hydrogen Bond ◽

Room Temperature ◽

Water Solubility ◽

Deep Eutectic Solvent ◽

Deep Eutectic Solvents ◽

Molar Ratio ◽

Hydrogen Bond Donor ◽

Hydrogen Bond Acceptor ◽

Natural Deep Eutectic Solvents ◽

Self Association

Turmeric contains curcumin as one of the active constituents, which gives yellow color and possesses lots of pharmacological actions. Even though curcumin has lots of pharmacological actions till now, it has not been approved as a medicine due to its low water solubility, permeability, and poor bioavailability. Deep eutectic solvent (DES) can be prepared by simply mixing two or more solid components, [among the two one is hydrogen bond donor (HBD) and another is hydrogen bond acceptor (HBA)] at a definite molar ratio where the solid components by self-association converted into a liquid at room temperature (RT). Natural deep eutectic solvents (NADES) are a specific subgroup of DES containing primary plant-based metabolites such as organic acids, alcohols, amino acids, or sugars. In this work, natural hydrophobic DESs were prepared with Camphor, Menthol, and Thymol. This was prepared from different ratios of Menthol:Thymol 1:1 to 1:5 and 1:1 to 5:1 (MT-DES); Camphor:Thymol 1:1 to 1:5 and 1:1 to 5:1 (CT-NADES); Camphor:Menthol 1:1 to 1:5 and 1:1 to 2:1 (CM-NADES). The pH and viscosity of prepared DESs were determined with the help of a digital pH meter and Brookfield viscometer. The solubility of curcumin in different NADESs was determined at room temperature (RT) to higher temperatures. The formation of different clear DES was obtained with slight heat. There was no difference in pH for the NADESs prepared without and with heat. Regarding the viscosity CM-DES (1:1) showed less viscosity when compared to other NADESs. The solubility of curcumin was found to be nearly double when it was dissolved in NADES for 1 hr at 35-40°C compared to 48 h stirring at 500 rotations per minute (rpm) at RT. Among different NADESs, curcumin solubility was found to be more in CM (1:1) ratio when compared to other NADESs.

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