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Wang X, Feng S, Song H. Caffeic Acid Phenethyl Ester Encapsulated in Self-Assemble Rice Peptides Nanoparticles: Storage Stability, In Vitro Release, and Their Interaction Mechanisms. Foods 2024; 13:755. [PMID: 38472867 DOI: 10.3390/foods13050755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Caffeic acid phenethyl ester (CAPE) is an important active component of propolis with many bioactivities. However, its efficiency and practical application are restricted due to its poor aqueous solubility and storage stability. In this study, a nanocarrier was fabricated to encapsulate CAPE using self-assembled rice peptides obtained by controllable enzymolysis. The physicochemical properties, encapsulation efficiency, and loading capacity of rice peptides nanoparticles (RPNs) were characterized. The storage stability, in vitro release, and interaction mechanisms between CAPE and RPNs were investigated. The results showed that RPNs, mainly assembled by disulfide bonds and hydrogen bonds, possessed an effective diameter of around 210 nm and a high encapsulation efficiency (77.77%) and loading capacity (3.89%). Importantly, the water solubility of CAPE was increased by 45 times after RPNs encapsulation. Moreover, RPNs encapsulation also significantly increased CAPE stability, about 1.4-fold higher than that of unencapsulated CAPE after 18-day storage. An in vitro release study demonstrated that RPNs could delay the release of CAPE, implying a better CAPE protection against extreme environments during digestion. Hydrogen bond and van der Waals force are the predominant interaction forces between RPNs and CAPE. Therefore, the newly developed nanoparticle is a potential delivery system that could effectively improve the aqueous solubility and stability of CAPE.
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Affiliation(s)
- Xinyue Wang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Siyi Feng
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Hongdong Song
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai 200093, China
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Arab N, Fotouhi L, Shokouhi M, A Mehrgardi M, Salis A. A multichannel closed bipolar platform to visual electrochemiluminescence sensing of caffeic acid as a model: Potential for multiplex detection. Anal Chim Acta 2024; 1287:342087. [PMID: 38182342 DOI: 10.1016/j.aca.2023.342087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 11/25/2023] [Accepted: 11/28/2023] [Indexed: 01/07/2024]
Abstract
In this study, a fully-featured electrochemiluminescence (ECL) sensing platform based on a multichannel closed bipolar system (closed-BP, C-BP) for the determination of caffeic acid (CA) was successfully developed. The system comprises three individual reservoirs connected to each other by two pairs of gold rods as bipolar electrodes. Moreover, a single pair of gold rods functions as the driving electrodes. Due to configuration consisting of three channels and double-bipolar electrodes, the detection of CA was accomplished in two oxidation and reduction pathways within a single device. Firstly, through close observation of the reactions occurring within the device and utilizing a universal pH indicator and bipolar electrodes, a precise mechanism for the current bipolar systems was initially proposed. Then, the concentration of CA was monitored in the reporting chamber through the following ECL intensities resulting from luminol oxidation and H2O2. The monitoring process was performed using both a photomultiplier tube (PMT) and a digital camera. In the process of analyte oxidation, the PMT and visual (camera)-based detection exhibited a linear response from 5 μmol L-1 to 700 μmol L-1 (limit of detection (LOD) 1.2 μmol L-1) and 50 μmol L-1 to 600 μmol L-1 (LOD 14.8 μmol L-1), respectively. In the analyte reduction pathway, the respective values were 30 μmol L-1 to 450 μmol L-1 (LOD 8.6 μmol L-1) and 55 μmol L-1 to 400 μmol L-1 (LOD 21.2 μmol L-1), for the PMT and visual-based detection, respectively. Our experiments have demonstrated the practical application of the sensor array for efficient and high-performance analysis. This innovative design holds significant potential for diverse fields and paves the way for the development of a user-friendly device.
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Affiliation(s)
- Nastaran Arab
- Department of Analytical Chemistry, Faculty of Chemistry, Alzahra University, Tehran, Iran
| | - Lida Fotouhi
- Department of Analytical Chemistry, Faculty of Chemistry, Alzahra University, Tehran, Iran; Analytical and Bioanalytical Research Centre (ABRC), Alzahra University, Tehran, Iran.
| | - Maryam Shokouhi
- Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran
| | - Masoud A Mehrgardi
- Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran
| | - Andrea Salis
- Department of Chemical and Geological Sciences, University of Cagliari, CSGI & CNBS, Cittadella Universitaria, SS 554 Bivio Sestu, 09042, Monserrato, CA, Italy
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Zhong Q, Reyes-Jurado F, Calumba KF. Structured soft particulate matters for delivery of bioactive compounds in foods and functioning in the colon. SOFT MATTER 2024; 20:277-293. [PMID: 38090993 DOI: 10.1039/d3sm00866e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
The present review discusses challenges, perspectives, and current needs of delivering bioactive compounds (BCs) using soft particulate matters (SPMs) for gut health. SPMs can entrap BCs for incorporation in foods, preserve their bioactivities during processing, storage, and gastrointestinal digestion, and deliver BCs to functioning sites in the colon. To enable these functions, physical, chemical, and biological properties of BCs are integrated in designing various types of SPMs to overcome environmental factors reducing the bioavailability and bioactivity of BCs. The design principles are applied using food grade molecules with the desired properties to produce SPMs by additionally considering the cost, sustainability, and scalability of manufacturing processes. Lastly, to make delivery systems practical, impacts of SPMs on food quality are to be evaluated case by case, and health benefits of functional foods incorporated with delivery systems are to be confirmed and must outweigh the cost of preparing SPMs.
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Affiliation(s)
- Qixin Zhong
- Department of Food Science, University of Tennessee, Knoxville, TN, USA.
| | | | - Kriza Faye Calumba
- Department of Food Science, University of Tennessee, Knoxville, TN, USA.
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Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma. Pharmaceutics 2023; 15:pharmaceutics15030901. [PMID: 36986762 PMCID: PMC10054442 DOI: 10.3390/pharmaceutics15030901] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.
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Synthesis, spectroscopic, chemical reactivity, molecular docking, DFT calculations and in-vitro anticancer activity studies of a novel ionic liquid; Metforminium ibuprofenate. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.120046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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6
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In vitro evaluation of antioxidant activity and biocompatibility of caffeic acid phenethyl ester loaded in polymeric micelles. Mol Cell Toxicol 2022. [DOI: 10.1007/s13273-022-00244-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Microemulsion Delivery System Improves Cellular Uptake of Genipin and Its Protective Effect against Aβ1-42-Induced PC12 Cell Cytotoxicity. Pharmaceutics 2022; 14:pharmaceutics14030617. [PMID: 35335992 PMCID: PMC8950416 DOI: 10.3390/pharmaceutics14030617] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 02/04/2023] Open
Abstract
Genipin has attracted much attention for its hepatoprotective, anti-inflammatory, and neuroprotection activities. However, poor water solubility and active chemical properties limit its application in food and pharmaceutical industries. This article aimed to develop a lipid-based microemulsion delivery system to improve the stability and bioavailability of genipin. The excipients for a genipin microemulsion (GME) preparation were screened and a pseudo-ternary phase diagram was established. The droplet size (DS), zeta potential (ZP), polydispersity index (PDI), physical and simulated gastrointestinal digestion stability, and in vitro drug release properties were characterized. Finally, the effect of the microemulsion on its cellular uptake by Caco-2 cells and the protective effect on PC12 cells were investigated. The prepared GME had a transparent appearance with a DS of 16.17 ± 0.27 nm, ZP of −8.11 ± 0.77 mV, and PDI of 0.183 ± 0.013. It exhibited good temperature, pH, ionic strength, and simulated gastrointestinal digestion stability. The in vitro release and cellular uptake data showed that the GME had a lower release rate and better bioavailability compared with that of free genipin. Interestingly, the GME showed a significantly better protective effect against amyloid-β (Aβ1-42)-induced PC12 cell cytotoxicity than that of the unencapsulated genipin. These findings suggest that the lipid-based microemulsion delivery system could serve as a promising approach to improve the application of genipin.
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Hong S, Dia VP, Baek SJ, Zhong Q. Nanoencapsulation of apigenin with whey protein isolate: physicochemical properties, in vitro activity against colorectal cancer cells, and bioavailability. Lebensm Wiss Technol 2022; 154:112751. [PMID: 34840350 PMCID: PMC8612601 DOI: 10.1016/j.lwt.2021.112751] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Incorporating lipophilic phytochemicals with anti-cancer activities in functional beverages requires an appropriate nanoencapsulation technology. The present objective was to encapsulate apigenin with whey protein isolate (WPI) utilizing a pH-cycle method and subsequently characterize physicochemical properties, the in vitro anticancer activities against human colorectal HCT-116 and HT-29 cancer cells, and the in vivo bioavailability. Up to 2.0 mg/mL of apigenin was nanoencapsulated with 1.0 mg/mL WPI, with an encapsulation efficiency of up to 98.15% and loading capacity of up to 196.21 mg/g-WPI. Nanodispersions were stable during storage, and apigenin became amorphous after encapsulation. Nanoencapsulation and in vitro digestion did not reduce the anti-proliferative activity of apigenin. Nanoencapsulation of apigenin enhanced the cellular uptake, the pro-apoptotic effects, and the bioavailability in the mice's blood and colon mucosa when comparing to the unencapsulated apigenin. Therefore, the present work may be significant to incorporate lipophilic phytochemicals in functional beverages for disease prevention.
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Affiliation(s)
- Shan Hong
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA
| | - Vermont P Dia
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA
| | - Seung Joon Baek
- College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea
| | - Qixin Zhong
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA,Corresponding Author: Department of Food Science, The University of Tennessee, 2510 River Drive, Knoxville, TN 37996, United States,
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Wang A, Leible M, Lin J, Weiss J, Zhong Q. Caffeic Acid Phenethyl Ester Loaded in Skim Milk Microcapsules: Physicochemical Properties and Enhanced In Vitro Bioaccessibility and Bioactivity against Colon Cancer Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:14978-14987. [PMID: 33140648 DOI: 10.1021/acs.jafc.0c05143] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Caffeic acid phenethyl ester (CAPE) has various biological activities but low water solubility and poor bioavailability. In this study, CAPE was encapsulated in skim milk powder (SMP) by spray drying warm aqueous ethanol solutions with different mass ratios of SMP and CAPE. The loading capacity and encapsulation efficiency were up to 10.1 and 41.7%, respectively. Differential scanning calorimetry and X-ray diffraction results confirmed the loss of crystallinity of CAPE after encapsulation. Fourier-transform infrared and fluorescence spectroscopy results indicated the hydrophobic binding between CAPE and caseins. Scanning electron microscopy and static light scattering results showed spherical capsules with an average diameter of around 26 μm. The CAPE loaded in SMP microcapsules showed significantly improved in vitro bioaccessibility and antiproliferation activity against human colon cancer cells compared to free CAPE. The simple, scalable, and low-cost approach in the present study may be significant for industrial encapsulation of CAPE and other lipophilic bioactive compounds.
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Affiliation(s)
- Anyi Wang
- Department of Food Science, University of Tennessee, Knoxville, Tennessee 37996, United States
| | - Malte Leible
- Department of Food Science, University of Tennessee, Knoxville, Tennessee 37996, United States
- Department of Food Science and Biotechnology, University of Hohenheim, Stuttgart 70174, Germany
| | - Jun Lin
- Department of Animal Science, University of Tennessee, Knoxville, Tennessee 37996, United States
| | - Jochen Weiss
- Department of Food Science and Biotechnology, University of Hohenheim, Stuttgart 70174, Germany
| | - Qixin Zhong
- Department of Food Science, University of Tennessee, Knoxville, Tennessee 37996, United States
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Bounegru AV, Apetrei C. Voltamperometric Sensors and Biosensors Based on Carbon Nanomaterials Used for Detecting Caffeic Acid-A Review. Int J Mol Sci 2020; 21:E9275. [PMID: 33291758 PMCID: PMC7730703 DOI: 10.3390/ijms21239275] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022] Open
Abstract
Caffeic acid is one of the most important hydroxycinnamic acids found in various foods and plant products. It has multiple beneficial effects in the human body such as antioxidant, antibacterial, anti-inflammatory, and antineoplastic. Since overdoses of caffeic acid may have negative effects, the quality and quantity of this acid in foods, pharmaceuticals, food supplements, etc., needs to be accurately determined. The present paper analyzes the most representative scientific papers published mostly in the last 10 years which describe the development and characterization of voltamperometric sensors or biosensors based on carbon nanomaterials and/or enzyme commonly used for detecting caffeic acid and a series of methods which may improve the performance characteristics of such sensors.
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Affiliation(s)
| | - Constantin Apetrei
- Department of Chemistry, Physics and Environment, Faculty of Sciences and Environment, “Dunărea de Jos” University of Galaţi, 47 Domnească Street, 800008 Galaţi, Romania;
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Singhvi G, Rapalli VK, Nagpal S, Dubey SK, Saha RN. Nanocarriers as Potential Targeted Drug Delivery for Cancer Therapy. ENVIRONMENTAL CHEMISTRY FOR A SUSTAINABLE WORLD 2020. [DOI: 10.1007/978-3-030-29207-2_2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Yordanov Y. Caffeic acid phenethyl ester (CAPE): cornerstone pharmacological studies and drug delivery systems. PHARMACIA 2019. [DOI: 10.3897/pharmacia.66.e38571] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Propolis is a natural product with a plethora of biological effects, utilized by traditional medicine since antiquity. However, its application as a pharmaceutical is hindered by its variable composition and difficult standardization. CAPE has been shown to be a major component of propolis, with a large contribution to its pharmacological effects, among which the anti-inflammatory, antioxidant and antineoplastic have been attracting most attention. The current review article aims to present the cornerstone pharmacological studies of CAPE throughout the years, following its discovery, which confirmed its primary importance among propolis constituents and opened the path to its intensive research as a potential pharmaceutical. We present the diversity of drug delivery systems of CAPE, which have been developed to improve its efficacy in in vitro and in vivo disease models and discuss their primary promises and weaknesses. The increased interest in recent years over more practical approaches of CAPE research such as its pharmaceutical formulation comes to show that it has a potential to become commercialized as a pharmaceutical.
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Li Q, Liu X, Wang X, Qiu S, Byambasuren K, Dang L, Wang Z. Antiproliferative Ability and Fluorescence Tracking of α-Linolenic Acid-Loaded Microemulsion as Label-Free Delivery Carriers in MDA-MB-231 Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:11518-11526. [PMID: 31513385 DOI: 10.1021/acs.jafc.9b04972] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
In this work, the effects of α-linolenic acid (ALA) loaded in oil-in-water (O/W) and water-in-oil-in-water (W/O/W) microemulsions on cell viability, lactic dehydrogenase (LDH) viability, and reactive oxygen species (ROS) levels were examined using Cell Counting Kit-8 (CCK-8), an LDH assay kit, and a fluorescence microscope, respectively. The CCK-8 assay demonstrated that ALA inhibited MDA-MB-231 human breast cancer cell proliferation in a dose-dependent manner. Further, the results of LDH activity and ROS levels revealed that ALA-induced cancer cell damage was closely related to oxidative stress. Under the irradiation of ultraviolet light, the microemulsion without any added fluorescent dye would emit bright blue fluorescence, and the fluorescent images of the cells treated with ALA-loaded O/W and W/O/W microemulsions at different incubation times were taken, which exhibited long-term photostability and biocompatibility. In addition, the fluorescence mechanism of the microemulsion was explained by immobilizing surfactant molecules with aggregation-induced emission (AIE) properties at the water-oil interface through the microemulsion with a self-assembled structure. These findings showed the potential application of O/W and W/O/W microemulsions as the label-free delivery carriers in long-term imaging of living cells and real-time release monitoring of nutrients.
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Affiliation(s)
- Qing Li
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
| | - Xiaoxue Liu
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
| | - Xueping Wang
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
| | - Shuang Qiu
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
| | | | - Leping Dang
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
| | - Zhanzhong Wang
- School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China
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