Special Issue "Polymers and Drug Delivery Systems"

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (31 March 2021).

Special Issue Editor

Prof. Dr. Iolanda De Marco
E-Mail Website
Guest Editor
Industrial Engineering Department, University of Salerno, Via Giovanni Paolo II, 132, I-84084 Fisciano (Salerno), Italy
Interests: polymer/active principle composites; drug delivery; supercritical carbon dioxide; microparticles and nanoparticles precipitation; biopolymer aerogels; polymer/drug coprecipitation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biocompatible natural and synthetic polymers are commonly used for drug delivery. Depending on the specific application, a modified release of the drug is frequently required, considering that the bioavailability of the active principal depends on its dissolution rate. If an active principal is scarcely soluble in water and a fast release is required, a hydrosoluble polymer can be used as carrier for the drug to enhance its dissolution rate. Contrariwise, controlled or sustained drug release obtained with the aid of hydrophobic polymers can be used to extend the active principle release, reducing the number of administrations. Additionally, the release of the drug at or near a specific site of action can be reached with targeted release products. In all these novel formulations, the characteristics of the final product strongly depend on the choice of the polymeric carrier.

The aim of this Special Issue is to collect research and review papers on different polymer/drug composites. Polymer/drug microparticles to obtain tablets or granules for oral suspensions, polymeric capsules containing the active principle, loaded foams, membranes, or aerogels for topical delivery are welcome.

Prof. Dr. Iolanda De Marco
Guest Editor

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Keywords

  • polymer/drug composites
  • fast, controlled or prolonged release
  • targeted delivery
  • natural and synthetic polymers
  • bioavailability
  • coprecipitated microparticles
  • drug loaded aerogels and foams
  • capsules for active principle delivery

Published Papers (12 papers)

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Research

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Article
Formation of Rutin–β-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation
Polymers 2021, 13(2), 246; https://doi.org/10.3390/polym13020246 - 13 Jan 2021
Cited by 1 | Viewed by 525
Abstract
In this work, rutin (RUT)–β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± [...] Read more.
In this work, rutin (RUT)–β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± 2.12 µm. The formation of RUT–β-CD inclusion complexes has been proved by different analyses, including Fourier transform infrared spectroscopy, Differential Scanning Calorimetry, X-ray diffraction, and UV-vis spectroscopy. The dissolution tests reveal a significant improvement in the release rate of RUT from inclusion complexes. Indeed, compared to the unprocessed RUT, the dissolution rate is about 3.9 and 2.4 times faster in the case of the complexes RUT–β-CD 1:2 and 1:1 mol:mol, respectively. From a pharmaceutical/nutraceutical point of view, CD-based inclusion complexes allow the reduction of the polymer amount in the SAS composite formulations. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications
Polymers 2020, 12(12), 2996; https://doi.org/10.3390/polym12122996 - 16 Dec 2020
Cited by 1 | Viewed by 550
Abstract
Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment [...] Read more.
Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route
Polymers 2020, 12(11), 2589; https://doi.org/10.3390/polym12112589 - 04 Nov 2020
Cited by 3 | Viewed by 710
Abstract
In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in [...] Read more.
In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain–blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood–brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Poly (Lactic-co-Glycolic Acid) Nanoparticles and Nanoliposomes for Protein Delivery in Targeted Therapy: A Comparative In Vitro Study
Polymers 2020, 12(11), 2566; https://doi.org/10.3390/polym12112566 - 01 Nov 2020
Cited by 3 | Viewed by 782
Abstract
Over the previous years, the design, development, and potential application of nanocarriers in the medical field have been intensively studied for their ability to preserve drug properties, especially their pharmacological activity, and to improve their bioavailability. This work is a comparative study between [...] Read more.
Over the previous years, the design, development, and potential application of nanocarriers in the medical field have been intensively studied for their ability to preserve drug properties, especially their pharmacological activity, and to improve their bioavailability. This work is a comparative study between two different types of nanocarriers, poly (lactic-co-glycolic acid)-based nanoparticles and phosphatidylcholine-based nanoliposomes, both prepared for the encapsulation of bovine serum albumin as a model protein. Polymeric nanoparticles were produced using the double emulsion water-oil-water evaporation method, whereas nanoliposomes were obtained by the thin-film hydration method. Both nanocarriers were characterized by morphological analysis, particle mean size, particle size distribution, and protein entrapment efficiency. Invitro release studies were performed for 12 days at 37 °C. In order to explore a possible application of these nanocarriers for a targeted therapy in the cardiovascular field, hemolytic activity and biocompatibility, in terms of cell viability, were performed by using human red blood cells and EA.hy926 human endothelial cell line, respectively. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Highly Enhanced Curcumin Delivery Applying Association Type Nanostructures of Block Copolymers, Cyclodextrins and Polycyclodextrins
Polymers 2020, 12(9), 2167; https://doi.org/10.3390/polym12092167 - 22 Sep 2020
Cited by 2 | Viewed by 861
Abstract
The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four [...] Read more.
The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four Pluronics (94, 105, 127,108) with different compositions led to the conclusion that solubilization capacity is maximum for Pluronic 105 with intermediate polarity (hydrophilic/lipophilic balance (HLB) = 15) possessing the optimum balance between capacity of hydrophobic core of the micelle and hydrophilic stabilizing shell of the associate. Curcumin concentration in aqueous solution was managed to increase 105 times up to 1–3 g/L applying Pluronic at 0.01 mol/L. Formation of a host–guest complex of cyclodextrin as another way of increasing the curcumin solubility was also tested. Comparing the(2-hydroxypropyl)-α, β and γ cyclodextrins (CD) with 6, 7 and 8 sugar units and their polymers (poly-α-CD, poly-β-CD, poly-γ-CD) the γ-CD with the largest cavity found to be the most effective in curcumin encapsulation approaching the g/L range of concentration. The polymer type of the CDs presented prolonged and pH dependent release of curcumin in the gastrointestinal (GI) system modelled by simulated liquids. This retarding effect of polyCD was also shown and can be used for tuning in the combined system of Pluronic micelle and polyCD where the curcumin release was slower than from the micelle. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts
Polymers 2020, 12(8), 1695; https://doi.org/10.3390/polym12081695 - 29 Jul 2020
Cited by 5 | Viewed by 961
Abstract
Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment [...] Read more.
Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen
Polymers 2020, 12(7), 1516; https://doi.org/10.3390/polym12071516 - 08 Jul 2020
Cited by 5 | Viewed by 1022
Abstract
Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low [...] Read more.
Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Article
Elaboration of Charged Poly(Lactic-co-Glycolic Acid) Microparticles for Effective Release of Tranexamic Acid
Polymers 2020, 12(4), 808; https://doi.org/10.3390/polym12040808 - 04 Apr 2020
Viewed by 1504
Abstract
In this study, tranexamic acid (TA) was used as a model compound to study the charge effect on the physicochemical properties of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). Charged PLGA MPs were elaborated by the incorporation of a quaternary ammonium, cetyltrimethylammonium bromide (CTAB), during [...] Read more.
In this study, tranexamic acid (TA) was used as a model compound to study the charge effect on the physicochemical properties of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). Charged PLGA MPs were elaborated by the incorporation of a quaternary ammonium, cetyltrimethylammonium bromide (CTAB), during the double emulsion solvent evaporation process. Three TA-CTAB-carrying modes of PLGA MPs were designed in the CTAB-free (TA-MP), adsorption (TA-CTABAD), or encapsulation (TA-CTABEN) form. The obtained MPs were characterized by morphology and TA-MP affinity. The experiment revealed that the three prepared MPs were spherical and smooth, with pores on their surfaces. TA-CTABAD had a relatively narrow size distribution, compared with that of TA-MP and TA-CTABEN. The particle sizes of TA-MP, TA-CTABEN, TA-CTABAD were measured as 59 ± 17, 54 ± 20, and 19 ± 8 μm, respectively. The zeta potential of the three MPs was found to be in the order: TA-CTABAD > TA-CTABEN > TA-MP. Differential scanning calorimetry (DSC) indicated that the manufacturing process had no influence on the glass transition temperature of the MPs, which was close to 48 °C. Thermogravimetric analysis illustrated that the presence of CTAB slightly changed the thermal stability of PLGA MPs. In vitro release showed that TA-CTABAD exhibited faster TA release than TA-MP and TA-CTABEN in a basic environment (pH of 13), probably because of electrostatic attraction. At pH = 1, the release of TA from TA-CTABEN was faster than those from TA-MP and TA-CTABAD, probably because of electrostatic repulsion. However, the effect of electrostatic interaction was not significant at pH = 7.4. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Review

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Review
Classification and Production of Polymeric Foams among the Systems for Wound Treatment
Polymers 2021, 13(10), 1608; https://doi.org/10.3390/polym13101608 - 16 May 2021
Cited by 1 | Viewed by 646
Abstract
This work represents an overview on types of wounds according to their definition, classification and dressing treatments. Natural and synthetic polymeric wound dressings types have been analyzed, providing a historical overview, from ancient to modern times. Currently, there is a wide choice of [...] Read more.
This work represents an overview on types of wounds according to their definition, classification and dressing treatments. Natural and synthetic polymeric wound dressings types have been analyzed, providing a historical overview, from ancient to modern times. Currently, there is a wide choice of materials for the treatment of wounds, such as hydrocolloids, polyurethane and alginate patches, wafers, hydrogels and semi-permeable film dressings. These systems are often loaded with drugs such as antibiotics for the simultaneous delivery of drugs to prevent or cure infections caused by the exposition of blood vessel to open air. Among the presented techniques, a focus on foams has been provided, describing the most diffused branded products and their chemical, physical, biological and mechanical properties. Conventional and high-pressure methods for the production of foams for wound dressing are also analyzed in this work, with a proposed comparison in terms of process steps, efficiency and removal of solvent residue. Case studies, in vivo tests and models have been reported to identify the real applications of the produced foams. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Review
Nanocellulose in Drug Delivery and Antimicrobially Active Materials
Polymers 2020, 12(12), 2825; https://doi.org/10.3390/polym12122825 - 27 Nov 2020
Cited by 13 | Viewed by 1252
Abstract
In recent years, nanocellulose (NC) has also attracted a great deal of attention in drug delivery systems due to its unique physical properties, specific surface area, low risk of cytotoxicity, and excellent biological properties. This review is focused on nanocellulose based systems acting [...] Read more.
In recent years, nanocellulose (NC) has also attracted a great deal of attention in drug delivery systems due to its unique physical properties, specific surface area, low risk of cytotoxicity, and excellent biological properties. This review is focused on nanocellulose based systems acting as carriers to be used in drug or antimicrobial delivery by providing different but controlled and sustained release of drugs or antimicrobial agents, respectively, thus showing potential for different routes of applications and administration. Microorganisms are increasingly resistant to antibiotics, and because, generally, the used metal or metal oxide nanoparticles at some concentration have toxic effects, more research has focused on finding biocompatible antimicrobial agents that have been obtained from natural sources. Our review contains the latest research from the last five years that tested nanocellulose-based materials in the field of drug delivery and antimicrobial activity. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Review
Microbial Exopolysaccharides as Drug Carriers
Polymers 2020, 12(9), 2142; https://doi.org/10.3390/polym12092142 - 19 Sep 2020
Cited by 3 | Viewed by 1054
Abstract
Microbial exopolysaccharides are peculiar polymers that are produced by living organisms and protect them against environmental factors. These polymers are industrially recovered from the medium culture after performing a fermentative process. These materials are biocompatible and biodegradable, possessing specific and beneficial properties for [...] Read more.
Microbial exopolysaccharides are peculiar polymers that are produced by living organisms and protect them against environmental factors. These polymers are industrially recovered from the medium culture after performing a fermentative process. These materials are biocompatible and biodegradable, possessing specific and beneficial properties for biomedical drug delivery systems. They can have antitumor activity, they can produce hydrogels with different characteristics due to their molecular structure and functional groups, and they can even produce nanoparticles via a self-assembly phenomenon. This review studies the potential use of exopolysaccharides as carriers for drug delivery systems, covering their versatility and their vast possibilities to produce particles, fibers, scaffolds, hydrogels, and aerogels with different strategies and methodologies. Moreover, the main properties of exopolysaccharides are explained, providing information to achieve an adequate carrier selection depending on the final application. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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Review
The Use of Poly(N-vinyl pyrrolidone) in the Delivery of Drugs: A Review
Polymers 2020, 12(5), 1114; https://doi.org/10.3390/polym12051114 - 13 May 2020
Cited by 37 | Viewed by 1792
Abstract
Polyvinylpyrrolidone (PVP) is a hydrophilic polymer widely employed as a carrier in the pharmaceutical, biomedical, and nutraceutical fields. Up to now, several PVP-based systems have been developed to deliver different active principles, of both natural and synthetic origin. Various formulations and morphologies have [...] Read more.
Polyvinylpyrrolidone (PVP) is a hydrophilic polymer widely employed as a carrier in the pharmaceutical, biomedical, and nutraceutical fields. Up to now, several PVP-based systems have been developed to deliver different active principles, of both natural and synthetic origin. Various formulations and morphologies have been proposed using PVP, including microparticles and nanoparticles, fibers, hydrogels, tablets, and films. Its versatility and peculiar properties make PVP one of the most suitable and promising polymers for the development of new pharmaceutical forms. This review highlights the role of PVP in drug delivery, focusing on the different morphologies proposed for different polymer/active compound formulations. It also provides detailed information on active principles and used technologies, optimized process parameters, advantages, disadvantages, and final applications. Full article
(This article belongs to the Special Issue Polymers and Drug Delivery Systems)
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