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JOURNAL OF MOLECULAR STRUCTURE · 2023 · IF 3.8

Insight into the inclusion mechanisms of curcumin in β-cyclodextrin using a screening strategy: Molecular simulation and experimental study

Meng Song,Chaokang Chang,Meng Wang,Lei Wang,Fang He,Sizhu Wu

Materials Studio 2018 software was used to model β -cyclodextrin ( β -CD) and 16 flavonoids, and Auto Dock 4.0 was used for molecular docking. From the molecular dynamics simulations, curcumin (CUR) was identified as the most suitable inclusion in β -CD. For comparison, the inclusion of CUR in 2, 6-dimethyl- β -cyclodextrin (DM- β -CD) and 2-hydroxypropyl- β -cyclodextrin (HP- β -CD) was simulated. The calculated parameters included solubility parameters, binding energy, mean square displacement, radial distribution, and hydrogen bonding. The simulation results showed that DM- β -CD was most effective for the inclusion of CUR. Inclusion complexes of CUR with β -CD, DM- β -CD, and HP- β -CD were prepared by freeze-drying. The inclusion complexes were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and UV-visible (UV-vis) spectra. The experimental results also showed that DM- β -CD was most effective for the inclusion of CUR, which is in agreement with the simulation results.

CAS / MDL: 111689-03-3
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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

Dialdehyde xanthan gum and curcumin synergistically crosslinked bioprosthetic valve leaflets with anti-thrombotic, anti-inflammatory and anti-calcification properties

Mengyue Hu,Xu Peng,Shubin Shi,Chang Wan,Can Cheng,Xixun Yu

Currently commercial glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) suffer from thromboembolic complications, calcification, and limited durability, which are the major stumbling block to wider clinical application of BVLs. Thus, developing new-style BVLs will be an urgent need to enhance the durability of BVLs and alleviate thromboembolic complications. In this study, a quick and effective collaborative strategy of the double crosslinking agents (oxidized polysaccharide and natural active crosslinking agent) was reported to realize enhanced mechanical, and structural stability, excellent hemocompatibility and anti-calcification properties of BVLs. Dialdehyde xanthan gum (AXG) exhibiting excellent stability to heat, acid-base, salt, and enzymatic hydrolysis was first introduced to crosslink decellularized porcine pericardium (D-PP) and then curcumin with good properties of anti-inflammatory, anti-coagulation, anti-liver fibrosis, and anti-atherosclerosis was used to synergistically crosslink and multi-functionalize D-PP to obtain AXG + Cur-PP. A comprehensive evaluation of structural characterization, hemocompatibility, endothelialization potential, mechanical properties and component stability showed that AXG + Cur-PP exhibited better anti-thrombotic properties and endothelialization potential, milder immune responses, excellent anti-calcification properties and enhanced mechanical properties compared with GA-crosslinked PP . Overall, this cooperative crosslinking strategy provides a novel solution to achieve BVLs with enhanced mechanical properties and excellent anti-coagulation, anti-inflammatory, anti-calcification, and the ability to promote endothelial cell proliferation .

CAS / MDL: 133232-56-1
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Carbohydrate Polymer Technologies and Applications · 2023 · IF 5.5

Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug

Zi-Dan Wang,Hu-Hong Peng,Dong-Qiang Lin,Yi-Xin Guan

Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H 2 O 2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.

CAS / MDL: 7244-02-2
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

The incorporated hydrogel of chitosan-oligoconjugated linoleic acid vesicles and the protective sustained release for curcumin in the gel

Huan Liu,Xinyu Meng,Lei Li,Yongmei Xia,Xueyi Hu,Yun Fang

Assemblies of as called “chitosan hydrogel-liposome” are expected for overcoming the burst effect in drug release from chitosan (CS) hydrogels. Herein, a hydrogel delivery system made of chitosan incorporated fatty acid vesicles was constructed for protective sustained release of curcumin (Cur). The curcumin was encapsulated in the prepared oligo-conjugated linoleic acid vesicles (OCLAVs), and then the drug-embedded vesicles were constructed to Cur-OCLAVs-CS hydrogels with CS solution. The fabricated Cur-OCLAVs-CS hydrogel was fluidic at room temperature and could be rapidly gelled at 37 °C. Morphology study proves that the OCLAVs stayed as nano-vesicles in the gel. The Cur-OCLAVs-CS hydrogels effectively declined the burst effect with enhanced antioxidant activity. The Cur (400 μM)-OCLAVs-CS gel presented a cumulative release rate of 51.23 % of curcumin in 96 h, comparing to 93.37 % of that from the Cur-CS gel. Moreover, the corporation of OCLAVs and CS made the gel exhibited strong synergistic effect on the antioxidant activity, with an enhancement of up to 148.1 % on the ferric reducing power. Therefore, the hydrogel carrier made of incorporated fatty acid vesicles-chitosan can be served as an injectable or 3D printable drug delivery system, which may provide a hint to overcome the burst effect that existed in chitosan and other polysaccharide-based gels.

CAS / MDL: 1898-66-4 28752-68-3
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Polymers · 2022 ·Vol. 15 ·期 1 ·116 · IF 4.967

The Dual Modification of PNIPAM and β-Cyclodextrin Grafted on Hyaluronic Acid as Self-Assembled Nanogel for Curcumin Delivery

Tisana Kaewruethai,Yuan Lin,Qian Wang,Jittima Amie Luckanagul

Curcumin is an extract of turmeric (Curcuma longa) which possesses anti-inflammatory, anti-cancer and wound-healing effects and has been used as an active compound in biomedical research for many years. However, its poor solubility presents challenges for its use in drug delivery systems. A modified nanogel delivery system, with PNIPAM and β-cyclodextrin grafted onto hyaluronic acid (PNCDHA), was utilized to enhance the solubility. The polymer was characterized by NMR, and the inclusion complex between curcumin and β-cyclodextrin was confirmed by FTIR. The potential of this PNCDHA polymer complex as a drug delivery vehicle was supported by a curcumin encapsulation efficiency of 93.14 ± 5.6% and the release of encapsulated curcumin at 37 °C. At a concentration of 0.5%w/vin water, PNCDHA nanogels were biocompatible with fibroblast cell line (L929) up to a curcumin concentration of 50 µM. There was a direct concentration between curcumin loading and cellular internalization. A more detailed study of the cellular internalization of PNCDHA nanogel should be considered in order to clarify cellular delivery mechanisms and to assess how its viability as a carrier may be optimized.Keywords:hyaluronic acid;β-cyclodextrin;PNIPAM;thermoresponsive;nanogel;self-assembly;curcumin

CAS / MDL: 25952-53-8 6066-82-6
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FOOD RESEARCH INTERNATIONAL · 2023 · IF 8.1

Fabrication of high strength cold-set sodium alginate/whey protein nanofiber double network hydrogels and their interaction with curcumin

Sijie Wu,Lu Wang,Yingying Zhao,Bilian Chen,Dan Qiu,Peilong Sun,Ping Shao,Simin Feng

Enhancing the bio-based hydrogels strength is fundamental to extend their engineering applications. In this study, high strength cold-set sodium alginate/whey protein nanofiber (SA/WPN) double network hydrogels were prepared and their interaction with curcumin (Cur) was studied. Our results indicated that the rheological and textural properties of SA/WPN double network hydrogels were enhanced with increasing WPN by forming SA-COO − -Ca 2+ - − OOC-WPN bridge through electrostatic interactions. The storage modulus (768.2 Pa), hardness (273.3 g), adhesiveness (318.7 g·sec) and cohesiveness (0.464) of SA/WPN50 (WPN concentration of 50 mg/mL) double network hydrogels were 3.75, 2.26, 3.76 and 2.19 times higher than those of SA hydrogels, respectively. Cur was combined with SA/WPN hydrogels through hydrogen bonding, van der Waals forces and hydrophobic interactions with an encapsulation efficiency of 91.6 ± 0.8 %, and the crystalline state was changed after binding. In conclusion, SA/WPN double network hydrogels can be enhanced by the addition of WPN and have potential as carriers for hydrophobic bioactive substances.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

Improving the physicochemical stability of Pickering emulsion stabilized by glycosylated whey protein isolate/cyanidin-3-glucoside to deliver curcumin

Xiaoya Tao,Cheng Chen,Yaochang Li,Xinguang Qin,Haizhi Zhang,Yuanyuan Hu,Zhengqi Liu,Xiaoming Guo,Gang Liu

Protein-polysaccharide-polyphenol delivery systems function as a promising tool to deliver bioactive ingredients aiming to improve their solubility and bioavailability. In this study, whey protein isolate (WPI), short-chain inulin (SCI), and cyanidin-3-glucoside (C3G) were first used to stabilize Pickering emulsions. The physicochemical properties and stability of curcumin encapsulated or not in Pickering emulsions were explored. Results showed that glycosylation and C3G reduced surface and interfacial tension on protein surfaces and inhibited the aggregation of emulsion droplets, thereby reducing the emulsion's particle size. WPI-SCI/C3G stabilized Pickering emulsion had the best stability. The CLSM results showed that the WPI-SCI and WPI-SCI/C3G stabilized emulsions were uniformly dispersed, suggesting that glycosylation and the interaction between protein and C3G enhanced the adsorption capacity of the interfacial protein and improved the stability of the Pickering emulsion. The retention rates of curcumin-loaded WPI-SCI- (67.34 %) and WPI-SCI/C3G- (77.07 %) stabilized Pickering emulsions on day 8 of storage were higher than those in WPI- (33.97 %) and WPI/C3G- (37.02 %) stabilized emulsions, and the degradation half-life was also extended from 7 days to >15 days. These findings provide a theoretical basis for the application of WPI Pickering emulsion and indicate a useful means for the delivery of bioactive components.

CAS / MDL: 3326-32-7 7385-67-3
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Folic acid-modified lactoferrin nanoparticles coated with a laminarin layer loaded curcumin with dual-targeting for ulcerative colitis treatment

Naijing Ye,Peng Zhao,Shibu Ayue,Shanshan Qi,Yan Ye,Haoqi He,Linxin Dai,Ruifeng Luo,Degui Chang,Fei Gao

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through β-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment.

CAS / MDL: 38215-36-0
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ENVIRONMENTAL TOXICOLOGY · 2023 · IF 4.5

Curcumin alleviates bisphenol AF-induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway

Ming Liu,Xu Zhou,Xiao-Jie Wang,Yong-Sheng Wang,Sheng-Ji Yang,Zhi-Ming Ding,Shou-Xin Zhang,Li-Dan Zhang,Ze-Qun Duan,Ai-Xin Liang,Li-Jun Huo

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

CAS / MDL: 458-37-7
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FOOD CHEMISTRY · 2023 · IF 8.8

Fabrication of compact zein-chondroitin sulfate nanocomplex by anti-solvent co-precipitation: Prevent degradation and regulate release of curcumin

Yufan Shi,Shuang Rong,Tingxian Guo,Ruyi Zhang,Duoxia Xu,Yahong Han,Fuguo Liu,Jiaqi Su,Hongxin Xu,Shuai Chen

The main purpose of this study was to prepare zein-chondroitin sulfate (ZC) nanocomplex by anti-solvent co-precipitation, and to encapsulate, protect and controlled-release curcumin. As the proportion of chondroitin sulfate (CS) increased, the particle size, turbidity and zeta-potential of the ZC nanocomplexes all increased. When the mass ratio of zein and CS was 10:3, the ZC nanocomplex had small particle size (129 nm) and low polydispersity index (0.3). According to FTIR, FS, CD and XRD results, zein and CS were tightly bound by electrostatic attraction, hydrophobic effect and hydrogen bonding. The ZC nanocomplex was designed to encapsulate curcumin with high encapsulation efficiency (94.7%) and loading capacity (3.8%), and also enhanced the resistance of curcumin to light and thermal degradation by 2.9 and 2.4 times. It also exhibited controlled release capability during simulated gastrointestinal digestion. These results suggested the ZC nanocomplex is a good delivery vehicle to facilitate the application of curcumin.

CAS / MDL: 9007-28-7 39455-18-0
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npj Science of Food · 2023 ·Vol. 7 ·期 1 ·1-10 · IF 6.4

Co-encapsulation of curcumin and quercetin with zein/HP-β-CD conjugates to enhance environmental resistance and antioxidant activity

Qiu Chao,Zhang Zhiheng,Li Xiaojing,Sang Shangyuan,McClements David Julian,Chen Long,Long Jie,Jiao Aiquan,Xu Xueming,Jin Zhengyu

In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein–cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein–cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.

CAS / MDL: 458-37-7 117-39-5
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Food Science and Human Wellness · 2022 · IF 8.022

The use of bacterial cellulose from kombucha to produce curcumin loaded Pickering emulsion with improved stability and antioxidant properties

Zhiyu Li,Wenxiu Hu,Jiajia Dong,Fidelis Azi,Xiao Xu,Chuanhai Tu,Sijie Tang,Mingsheng Dong

Curcumin is a bioactive molecule with limited industrial application because of its instability and poor solubility in water. Herein, curcumin-loaded Pickering emulsion was produced using purified bacterial cellulose from fermented kombucha (KBC). The morphology, particle size, stability, rheological properties, and antioxidant activities of the curcumin-loaded Pickering emulsion were investigated. The fluorescence microscope and scanning electron microscopy images showed that the curcumin-loaded Pickering emulsion formed circular droplets with good encapsulation. The curcumin-load Pickering emulsion exhibited better stability under a wide range of temperatures, low pH, sunlight, and UV-365 nm than the free curcumin, indicating that the KBC after high-pressure homogenization improved the stability of the CPE. The encapsulated curcumin retained its antioxidant capacity and exhibited higher functional potential than the free curcumin. The study demonstrated that the KBC could be an excellent material for preparing a Pickering emulsion to improve curcumin stability and antioxidant activity.

CAS / MDL: 59-02-9
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