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Curcumin
FOOD CHEMISTRY · 2022 · IF 9.231

Study on the stability and oral bioavailability of curcumin loaded (-)-epigallocatechin-3-gallate/poly(N-vinylpyrrolidone) nanoparticles based on hydrogen bonding-driven self-assembly

Yuanyuan Chen,Jingting Wang,Zhenan Rao,Junfeng Hu,Qiming Wang,Yueru Sun,Xiaojuan Lei,Jichun Zhao,Kaifang Zeng,Zhigang Xu,Jian Ming

The biological activity and absorption of curcumin (Cur) is limited in application due to its low water solubility, poor   stability   and rapid metabolism. In this work, Cur loaded (-)-epigallocatechin-3-gallate (EGCG)/poly( N -vinylpyrrolidone) (PVP) nanoparticles (CEP-NPs) was successfully fabricated via self-assembly driven by hydrogen bonding , providing with desirable Cur-loading efficiency, high stability, strong antioxidant capacity , and pH-triggered intestinal targeted release properties. Molecular dynamics simulations further indicated the Cur was coated with EGCG and PVP in CEP-NPs and high acid prolonged release property was attribute to low ionization degree of EGCG. Besides, the enhanced intestinal absorption of Cur was related to inhibition of Cur metabolism by EGCG, enhancement of cellular uptake and higher Caco-2 monolayer permeation. Pharmacokinetic study showed that the oral bioavailability presented nearly 12-fold increment. Therefore, this study provides a new horizon for improving the Cur utilization in food and pharmaceutical fields.

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Nanomaterials · 2022 ·Vol. 12 ·期 4 ·696 · IF 5.719

Affibody Modified G-quadruplex DNA Micelles Incorporating Polymeric 5-Fluorodeoxyuridine for Targeted Delivery of Curcumin to Enhance Synergetic Therapy of HER2 Positive Gastric Cancer

Chao Zhang,Shuangqing Fu,Fanghua Zhang,Mengnan Han,Xuming Wang,Jie Du,Honglei Zhang,Wei Li

Combination chemotherapy is emerging as an important strategy for cancer treatment with decreased side effects. However, chemotherapeutic drugs with different solubility are not easy to realize co-delivery in traditional nanocarriers. Herein, an affibody modified G-quadruplex DNA micellar prodrug (affi-F/GQs) of hydrophilic 5-fluorodeoxyuridine (FUdR) by integrating polymeric FUdRs into DNA strands is developed for the first time. To achieve synergistic efficacy with hydrophobic drugs, curcumin (Cur) is co-loaded into affi-F/GQs micelles to prepare the dual drug-loaded DNA micelles ([email protected]/GQs), in which affibody is employed as a targeting moiety to facilitate HER2 receptor-mediated uptake.[email protected]/GQs have a small size of approximately 130 nm and exhibit excellent stability. The system co-delivers FUdR and Cur in a ratiometric manner, and the drug loading rates are 21.1% and 5.6%, respectively. Compared with the physical combination of FUdR and Cur,[email protected]/GQs show higher cytotoxicity and greater synergistic effect on HER2 positive gastric cancer N87 cells. Surprisingly,[email protected]/GQs significantly enhance the expression and activity of apoptosis-associated proteins in Bcl-2/Bax-caspase 8, 9-caspase 3 apoptotic pathway, which is the main factor in the death of tumor cells induced by FUdR. Overall, this nanoencapsulation is a promising candidate for the targeted co-delivery of drugs with significant differences in solubility.Keywords:G-quadruplex;DNA micelles;affibody;5-fluorodeoxyuridine;curcumin;synergetic therapy

CAS / MDL: 458-37-7 129-00-0
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Food Bioscience · 2023 · IF 5.2

pH-driven preparation of caseinate-chitosan complex coacervation for co-encapsulation of hydrophobic curcumin and hydrophilic l-ascorbate: Stability and in vitro release properties

Xin Yin,Muhammad Aslam Khan,Paul Van der Meeren,Shuai Feng,Yongchao Wang,Li Liang

Co-encapsulation of bioactive compounds with different functionality in a carrier has received considerable attention, while co-encapsulation of bioactives with different solubility remains a challenge. In this study, the co-encapsulation of hydrophilic l -ascorbate and hydrophobic curcumin was achieved using an organic-free method. The aim of this work was to evaluate the efficacy of chitosan coating loaded with l -ascorbate on the complexation of curcumin with caseinate by investigating their interaction, storage stability and release behavior during simulated digestion. The size and ζ-potential of the optimized chitosan-caseinate binary particles at pH 5.0 were 582 nm and 28 mV, respectively. l -ascorbate electrostatically interacted with chitosan and then coated on the caseinate particles where hydrophobic curcumin was encapsulated. The encapsulation efficiency of curcumin and l -ascorbate was 96.2% and 47.6%, respectively. l -ascorbate-loaded chitosan coating significantly improved the storage and irradiation stability of curcumin and inhibited the structural changes of caseinate induced by the loaded curcumin after storage. The antioxidant activity of the co-delivered system was significantly improved compared with either individual system and basically unchanged during irradiation. These results may serve as a helpful guide for future study on the optimization of core-shell particles for the co-delivery of multiple bioactive compounds.

CAS / MDL: 28752-68-3
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FOOD RESEARCH INTERNATIONAL · 2020 · IF 4.972

Curcumin-loaded liposomes prepared from bovine milk and krill phospholipids: Effects of chemical composition on storage stability, in-vitro digestibility and anti-hyperglycemic properties

Yujie Wu,Bolin Mou,Shuang Song,Chin-Ping Tan,Oi-Ming Lai,Cai Shen,Ling-Zhi Cheong

Present study prepared curcumin liposomes with high encapsulation efficiency (>70%) using bovine milk and krill phospholipids; and investigated the effects of phospholipids composition on storage stability, in-vitro bioavailability, antioxidative and anti-hyperglycemic properties of the curcumin liposomes. Curcumin liposomes prepared from bovine milk phospholipids have smaller particle sizes (163.1 ± 6.42 nm) and greater negative zeta potentials (−26.7 mv) as compared to that prepared from krill phospholipids (particle size: 212.2 ± 4.1 nm, zeta potential: −15.23 mv). In addition, curcumin liposomes from bovine milk phospholipids demonstrated better stability under harsh storage conditions (alkaline conditions, oxygen, high temperature and relative humidity). Nevertheless, curcumin-loaded liposomes prepared from bovine milk phospholipids have inferior bioavailability compared to that prepared from krill phospholipids. No significant differences can be observed in terms of anti-oxidative and anti-hyperglycemic properties of liposomes prepared from both bovine milk and krill phospholipids. Findings from present study will open up new opportunities for development of stable curcumin liposomes with good functional properties (high digestibility, bioavailability and pharmacological effects).

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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2019 · IF 3.532

PEGylated lipid bilayer coated mesoporous silica nanoparticles co-delivery of paclitaxel and curcumin leads to increased tumor site drug accumulation and reduced tumor burden

Jiafeng Gao,Kai Fan,Yipeng Jin,Linna Zhao,Qian Wang,Yinian Tang,Huihao Xu,Zhongjie Liu,Shuaiyu Wang,Jiahao Lin,Degui Lin

Homogeneous PEGylated lipid bilayer coated highly ordered MSNs (PLMSNs) which were systematically optimized and characterized to co-encapsulate paclitaxel (Tax) and curcumin (Cur) were verified to manifest prolonged and enhanced cytotoxic effect against canine breast cancer cells in our previous study. In this article, we took further study of the pharmacokinetic property, cellular uptake, subcellular localization, in vivo distribution and tumor accumulation ability, and treatment efficacy of the drug delivery system . The results revealed that the delivery system could significantly increase the AUC of two drugs, and the anti-tumor effect showed that both intravenous and intratumoral administration group better controlled the tumor weight than that of other groups ( P  < .05), and the anti-tumor rates were 58.4% and 58.3% respectively. Cell uptake and localization study showed that PLMSNs could effectively carry drugs into cancer cells with sustained release characteristics. The subcellular localization of PLMSNs was mainly in lysosomes and mitochondria. In vivo fluorescence tracing results showed that PLMSNs could be effectively accumulated in the tumor site. The results revealed that the delivery system could effectively reduce the clinical dosage of drugs and reduce its toxic side effects, effectively carry drugs into cancer cells, and exhibit good targeting characteristics for breast cancer.

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ACS Sustainable Chemistry & Engineering · 2019 · IF 6.97

Effects of Degree of Polymerization on Size, Crystal Structure, and Digestibility of Debranched Starch Nanoparticles and Their Enhanced Antioxidant and Antibacterial Activities of Curcumin

Yang Qin,Jinpeng Wang,Chao Qiu,Yao Hu,Xueming Xu,Zhengyu Jin

The versatility of debranched starch nanoparticles (DBS-NPs) has attracted considerable attention from the food, agricultural, and cosmetic industries. The aim of this study was to investigate the effect of DBSs with low (DP < 10), moderate (10 > DP < 20), and high (20 > DP < 25) DPs (where DP represents the degree of polymerization), as well as reaction temperatures (25, 60, and 90 °C) on size, morphology, crystal structure, and digestibility of the refined DBS-NPs via nanoprecipitation. Spherical DBS-NPs with a controlled size of 40–200 nm were obtained; no nanoparticles were observed when the average DP was <10. The relative crystallinity increased from 11.1% to 71.6% as the increasing the average DP increased. When the microsized DBSs were converted to nanoscale DBSs, the rapidly digestible starch levels of the DBS-NPs decreased, and the DBS-NPs showed remarkable increase in the sum of slowly digestible starch and resistant starch contents, compared to the responding DBS. Furthermore, the maximum encapsulation efficiency of curcumin in DBS-NPs reached up to 92.49%. The antioxidant and antibacterial activities of curcumins in DBS-NPs were enhanced significantly, and their antioxidant stability was improved markedly when exposed to UV light or heat treatments.

CAS / MDL: 458-37-7
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JOURNAL OF MICROENCAPSULATION · 2019 · IF 2.04

Nano-encapsulation of curcumin using soy protein hydrolysates – tannic acid complexes regulated by photocatalysis: a study on the storage stability and in vitro release

Bei Jin,Xiaosong Zhou,Shanshan Zhou,Yuan Liu,Zhiyuan Zheng,Yuxin Liang,Siting Chen

Purpose: To evaluate the feasibility of soy protein hydrolysates (SPH)-tannic acid (TA) complex nanoparticle obtained by photocatalysis (SPH-T (P)) to construct curcumin (Cur) delivery vehicles.Methods: The interaction behaviour of SPH-T (P) was investigated using Fourier transform infra-red, X-ray diffraction and differential scanning calorimeter analyzes. Formation and stability of the complexes were characterised by particle size, morphology, zeta potential, and in vitro release.Results: Negatively charged Cur-loaded complex with small size (<100 nm), spherical cluster shape and uniform size distribution were formed through the driving force of electrostatic attraction, followed by hydrogen bonding. The presence of photocatalysis in the complexes significantly improved the storage stability and in vitro sustained release of curcumin by enhancing the hydrogen bonding, hydrophobic effects and π–π stacking interactions between SPH and TA.Conclusion: SPH-T (P) would be a useful and promising delivery vehicle for encapsulating, protecting, and delivering hydrophobic nutraceuticals.

CAS / MDL: 9001-62-1 1401-55-4
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Understanding the cellular uptake and biodistribution of a dual-targeting carrier based on redox-sensitive hyaluronic acid-ss-curcumin micelles for treating brain glioma

Cihui Tian,Sajid Asghar,Ziyi Hu,Yue Qiu,Jingwei Zhang,Feng Shao,Yanyu Xiao

The gliomas treatment is challenging due to the limits imposed by blood-brain barrier to the distribution of the drugs in the brain. Therefore, we designed a brain glioma targeting redox-sensitive hyaluronic acid (HA)-ss-curcumin (CUR) micelles . HA was conjugated to CUR through a disulfide bond , which could form micelles independently in aqueous solution. And we further increased the drug loading by loading free CUR. Brain penetration was achieved with Tween 80, whereas glioma-targeting was inclined by CD44-mediated endocytosis . Compared to the disulfide-free group, the redox-sensitive micelles exhibited rapid in vitro drug release under high glutathione conditions, significantly enhanced cell apoptosis and cellular uptake in G422 glioma cells. Redox-sensitive micelles displayed about 4.70-fold higher area under the curve in rats after intravenous injection in comparison to the free CUR and effectively accumulated in the brain. These findings suggest that redox-sensitive micelles could be a promising candidate to achieve brain targeted CUR delivery.

CAS / MDL: 7440-50-8
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Acta Pharmaceutica Sinica B · 2019 · IF 5.808

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects

Yan Chen,Chen Chen,Xiaojuan Zhang,Chuanchuan He,Pengxuan Zhao,Minsi Li,Ting Fan,Ruicong Yan,Yao Lu,Robert J. Lee,Muhammad Waseem Khan,Muhammad Sarfraz,Xiang Ma,Tan Yang,Guangya Xiang

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum–curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt– [email protected] ) to facilitate intracellular release and synergistic anti-cancer effects. Pt– [email protected] was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro . In addition, Pt– [email protected] blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt– [email protected] provided a novel and attractive therapeutic strategy for NSCLC.

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Cancer Management and Research · 2018 · IF 3.702

A mono-carbonyl analog of curcumin induces apoptosis in drug-resistant EGFR-mutant lung cancer through the generation of oxidative stress and mitochondrial dysfunction

Xuanxuan Dai,Junru Zhang,Guilong Guo,Yuepiao Cai,Ri Cui,Changtian Yin,Weidong Liu,Rajamanickam Vinothkumar,Tingting Zhang,Guang Liang,Xiaohua Zhang

Introduction Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. Materials and methods In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975. Results In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. Discussion These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC.

CAS / MDL: 184475-35-2
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FOOD AND CHEMICAL TOXICOLOGY · 2016 · IF 3.584

Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells

Chongshan Dai,Bin Li,Yan Zhou,Daowen Li,Shen Zhang,Hui Li,Xilong Xiao,Shusheng Tang

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress , mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX , a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.

CAS / MDL: 458-37-7
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Oncotarget · 2017 · IF 5.168

PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice

Na Huang,Shuai Lu,Xiao-Ge Liu,Jie Zhu,Yu-Jiong Wang,Rui-Tian Liu

Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.

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