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This study investigates the synergistic effects of alginate@montmorillonite (Alg@Mt) hybrid microcapsules for enhancing water purification, focusing on improving the encapsulation of hydrophobic contaminants. Alg@Mt microcapsules were prepared through ionotropic gelation. Characterisation was performed using SEM-EDX, FTIR, XRD, and TGA. Encapsulation efficiency (EE), loading capacity (LC), and release behaviour were also examined. Alg@Mt microcapsules effectively removed phenol and its chlorinated derivatives from water. Incorporating Na-Mt improved structural and thermal properties, EE, and LC. Increasing the clay content to 60% (w/w) raised the EE of phenol and its more hydrophobic derivative, 2,4,6-trichlorophenol, from 39.74 ± 3.1% (w/w) and 63.91 ± 2% (w/w) to 60.56 ± 1.6% (w/w) and 82.28 ± 2.3% (w/w), respectively, with more controlled release rates, following Fickian diffusion mechanism. EE increased with phenolic substances hydrophobicity, while LC and release rates were inversely related. This approach is promising for removing hydrophobic contaminants from water.

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The incorporation of active compounds into polymeric matrices using traditional methods has several drawbacks mainly due to the high volatility and thermal sensitivity of these substances. A solution to this problem could be the incorporation of bioactive compounds forming inclusion complexes as a strategy to improve the chemical stability, bioactivity and achieve controlled release. In this work, ß-cyclodextrin/carvacrol inclusion complex was prepared by spray drying to be incorporated into poly(lactic acid) (PLA) and Mater-Bi® films by supercritical CO2 impregnation. The impregnation process was carried out at pressures of 10, 15 and 20 MPa and at 40 °C. Both polymers showed the highest amount of incorporated inclusion complex at 15 MPa, where the percentage of impregnation varied from 0.6 % to 7.1 % in Mater-Bi® and PLA, respectively. Release tests for PLA films impregnated with inclusion complex showed a slow release of the active compound, which did not reach equilibrium after 350 h under the experimental conditions. This prolonged release was not observed in Mater-Bi® due to the lower incorporation of the inclusion complex. The release rate was described herein by a comprehensive phenomenological model considering the decomplexation kinetics combined with the equilibrium and mass transfer expressions.

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The role of anionic counterions of divalent metal salts in alginate gelation and hydrogel properties has been thoroughly investigated. Three anions were selected from the Hofmeister series, namely sulphate, acetate and chloride, paired in all permutations and combinations with divalent metal cations like calcium, zinc and copper. Spectroscopic analysis revealed the presence of anions and their interaction with the respective metal cations in the hydrogel. The data showed that the gelation time and other hydrogel properties were largely controlled by cations. However, subtle yet significant variations in viscoelasticity, water uptake, drug release and cytocompatibility properties were anion dependent in each cationic group. Computational modelling based study showed that metal-anion-alginate configurations were energetically more stable than the metal-alginate models. The in vitro and in silico studies concluded that acetate anions preceded chlorides in the drug release, swelling and cytocompatibility fronts, followed by sulphate anions in each cationic group. Overall, the data confirmed that anions are an integral part of the metal-alginate complex. Furthermore, anions offer a novel option to further fine-tune the properties of alginate hydrogels for myriads of applications. In addition, full exploration of this novel avenue would enhance the usability of alginate polymers in the pharmaceutical, environmental, biomedical and food industries.

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It was investigated whether loading multi-wall carbon nanotubes (CNTs) with two natural anticancer agents: ferulic acid (FUA) and diosgenin (DGN), may enhance the anticancer effect of these drugs. The CNTs were functionalized with carboxylic acid (CNTCOOH) or amine (CNTNH2), loaded with the above pro-drugs, as well as both combined and coated with chitosan or chitosan-stearic acid. Following physicochemical characterization, the drug-loading properties and kinetics of the drug's release were investigated. Their effects on normal human skin fibroblasts and MCF-7 breast carcinoma cells, HepG2 hepatocellular carcinoma cells, and A549 non-small-cell lung cancer cells were evaluated in vitro. Their actions at the molecular level were evaluated by assessing the expression of lncRNAs (HULC, HOTAIR, CCAT-2, H19, and HOTTIP), microRNAs (mir-21, mir-92, mir-145, and mir-181a), and proteins (TGF-ß and E-cadherin) in HepG2 cells. The release of both pro-drugs depended on the glutathione concentration, coating, and functionalization. Release occurred in two stages: a no-burst/zero-order release followed by a sustained release best fitted to Korsmeyer-Peppas kinetics. The combined nanoformulation cancer inhibition effect on HepG2 cancer cells was more pronounced than for A549 and MCF7 cells. The combined nanoformulations had an additive impact followed by a synergistic effect, with antagonism demonstrated at high concentrations. The nanoformulation coated with chitosan and stearic acid was particularly successful in targeting HepG2 cells and inducing apoptosis. The CNT functionalized with carboxylic acid (CNTCOOH), loaded with both FUA and DGN, and coated with chitosan-stearic acid inhibited the expression of lncRNAs and modulated both microRNAs and proteins. Thus, nanoformulations composed of functionalized CNTs dual-loaded with FUA and DGN and coated with chitosan-stearic acid are a promising drug delivery system that enhances the activity of natural pro-drugs.

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The intestine is not only the main accumulation organ of microplastics (MPs), but also the intestinal environment is very conductive to the release of additives in MPs. However, the kinetics of release process, influence factors, and the related effects on gut microbiota remain largely unknown. In this study, a mucosal-simulator of the human intestinal microbial ecosystem (M-SHIME) was used to investigate the influence of gut microbiota on the release of phthalates (PAEs) from MPs and the effects of MPs on the intestinal luminal microbiota and mucosal microbiota. We found that di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and dimethyl phthalate (DMP) were the dominant PAEs released in the gut. Gut microbiota accelerated the release of PAEs, with the time to reach the maximum release was shortened from 7 days to 2 days. Moreover, MPs induced differential effects on luminal microbiota and mucosal microbiota. Compared with mucosal microbiota, the luminal microbiota was more susceptible to the leaching of PAEs from MPs, as evidenced by more microbiota alterations. MPs also inhibited the metabolic activity of intestinal flora based on the reduced production of short chain fatty acids (SCFA). These effects were mainly contributed by the release of PAEs. Acidaminococcus and Morganella were simultaneously correlated to the release of PAEs and the inhibition of metabolic activity of intestinal microbiota and can be used as indicators for the intestinal exposure of MPs and additives.

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Designing strategies for an effective transformation of food waste into high-value products is a priority to address environmental sustainability concerns. Coffee silverskin is the major by-product of the coffee roasting industry, being rich in compounds with health benefits. Such composition gives it the potential to be transformed into high-value products. In this study, coffee silverskin extracts were enriched, regarding caffeine and chlorogenic acid contents, by adsorbent column chromatography. The compounds content increased 3.08- and 2.75-fold, respectively, compared to the original extract. The enriched fractions were loaded into nano-phytosomes or cholesterol-incorporated nano-phytosomes (first coating layers) to improve the physiochemical properties and permeation rate. These nano-lipid carriers were also subjected to a secondary coating with different natural polymers to improve protection and stability against degradation. In parallel, and for comparison, different natural polymers were also used as first coating layers. The produced particles were evaluated regarding product yield, encapsulation efficiency, loading capacity, particle size, surface charge, and in vitro release simulating gastrointestinal conditions. All samples exhibited anionic surface charge. FTIR and molecular docking confirmed interactions between the phytoconstituents and lipid bilayers. The best docking score was observed for 5-caffeoylquinic acid (chlorogenic acid) exhibiting a stronger hydrogen binding to the lipid bilayer. Among several kinetic models tested, the particle release mechanism fitted well with the First-order, Korsmeyer-Peppas, and Higuchi models. Moreover, most of the formulated particles followed the diffusion-Fick law and anomalous transport.

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The orthodontic kinetic release of metal ions was studied in order to have a conclusive in vivo data for variation of metal ion concentrations with time (month) at normal oral temperature 37°C, which affects the saliva quality and quantity, pH, and chemical and physical characteristics of food and liquid. The superficial breakdown and release of metals from the alloy brackets were investigated by scanning electron microscopy (SEM) and energy dispersive X-Ray spectroscopy (EDS) images. The kinetic release experiment of the metal ion concentrations (nickel, chromium, titanium, iron, and copper) in the saliva uptakes follows a pseudo-second-order kinetic model; the release rate of metal ions was in series Fe2+ > Ti2+ > Ni2+ > Cu2+ > Cr3+, and the highest saliva pH and flow rate were detected after 1 month for fixed orthodontics appliance was (7.16 ± 0.55) and (0.88 ± 0.55) respectively.

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The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer co-loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA-TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.

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In this study we developed electrospun cellulose acetate nanofibers (CANFs) that were loaded with a model non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, Ib) and coated with poly(acrylamide) (poly-AAm) hydrogel polymer using two consecutive steps: an electrospinning process followed by photopolymerization of AAm. Coated and non-coated CANF formulations were characterized by several microscopic and spectroscopic techniques to evaluate their physicochemical properties. An analysis of the kinetic release profile of Ib showed noticeable differences due to the presence or absence of the poly-AAm hydrogel polymer. Poly-AAm coating facilitated a constant release rate of drug as opposed to a more conventional burst release. The non-coated CANFs showed low cumulative drug release concentrations (ca. 35 and 83% at 5 and 10% loading, respectively). Conversely, poly-AAm coated CANFs were found to promote the release of drug (ca. 84 and 99.8% at 5 and 10% loading, respectively). Finally, the CANFs were found to be superbly cytocompatible.

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Core/shell electrospun mats based on cellulose acetate (CA) and polycaprolactone (PCL) were developed as novel active materials for releasing quercetin (Quer) and curcumin (Cur). The effect of polymeric uniaxial and coaxial electrospun systems and the chemical structures of Quer and Cur on the structural, thermal, and mass transfer properties of the developed mats were investigated. Release modelling indicated that the diffusion of the active agents from the uniaxial PCL fibers was highly dependent on the type of food simulant. Higher diffusion coefficients were obtained for both active agents in acid food simulant due to the higher swelling of the electrospun mats. In addition, CA/PCL coaxial structures slowed down the diffusion of both active agents into both food simulants. CA increased the retention of the active compounds in the polymer structure, resulting in partition coefficients values higher than the values obtained for uniaxial active PCL mats.

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PAMAM dendrimers (PAMs) are a group of polymeric macromolecules with distinctive physicochemical features, which can make them multifunctional theranostic nanoparticles (NPs). This study was designed to examine the impact of mucin-1 aptamer-conjugated NPs which were engineered using PAM for image-guided delivery of gefitinib (GEF) in the breast cancer cells/tumor. For this, PAMAM was conjugated with diethylenetriaminepentaacetic acid (DTPA) and modified with PEG2000 to prepare a multi-functionalized NPs. Subsequently, GEF was loaded onto the DTPA-PAM-PEG NPs, which were then armed with MUC-1 aptamer to form the DTPA-PAM-PEG/GEF@MUC-1 nanosystem. Finally, aptamer-conjugated NPs were radiolabeled by gallium-67 as an imaging agent to construct image-guided nanoplatforms. The prepared NPs were characterized by different techniques. The kinetic release models of gefitinib from radiolabeled NPs offer the sustained-release mechanism of the encapsulated drug for over 7 days. In vitro evaluation showed higher cytotoxicity and enhanced uptake of the mucin-grafted NPs in MCF-7 cells. Nuclear medicine imaging and in vivo investigations revealed significant accumulation of 67Ga-DTPA-PAM-PEG/GEF@MUC-1 in the tumor site of the animal models. These data suggest that the engineered NPs are a promising image-guided nanosystem for mucin-expressing breast cells/tumors with the assistance of nuclear medicine.

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Indomethacin is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) that are widely prescribed drug for pain and inflammation. However, its notoriety of causing gastrointestinal effect, low water solubility, and its short half-life would affect patient compliance and its oral absorption and accordingly justify the need to develop a formula with a controlled and sustained release manner in combination with anti-ulcer drugs. Herein, we synthesized indomethacin-paracetamol co-drug loaded in nanoemulsion and encapsulated in famotiditine loaded polycaprolactone (PCL) nanoparticles. The synthesis of the co-drug was achieved by the formation of a hydrolyzable ester between the indomethacin and paracetamol. The synthesized co-drug was preloading in nanoemulsion (Co-NE), which encapsulated into famotidine PCL nanoparticles utilizing the nanoprecipitation approach. The developed nanosystem showed hydrodynamic size less than 200 nm and the zeta potential value above -30 mV. TEM images confirmed the morphological structure of the formed nanoemulsion and the loaded PCL nanoparticles. Stability studies revealed that the developed nanosystem was stable at different temperatures and pHs over 1 month. Moreover, improvement of the solubilities of these three drugs leading to have a controlled-release multicomponent system of both co-drug and famotidine over 3 days. This multicomponent nanoparticle might be a potential platform to overcome the obstacles of NSAIDs, synergize drugs with different mechanisms of actions by co-encapsulating a small-sized nanoemulsion into PCL nanoparticles for reaching the goal of effective anti-inflammatory therapy.

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The present work aims to encapsulate goby fish protein hydrolysate (GPH), endowed with antioxidant activity, through ionic gelation process using blue crab chitosan (CH) and tripolyphosphate anions and to evaluate the structural, thermal and antioxidant properties of the elaborated microparticles (MPs). The GPH-loaded MPs present spherical shape as seen by scanning electron microscopy (SEM) images and positive zeta potential. The increase of loaded GPH concentration led to the increase of encapsulation efficiency (EE) and to the reduction of the particle size. In fact, MPs, loaded with 2 and 5 mg/ml GPH, had EE values of 44 and 58% and mean particles size of 4.81 and 3.78 µm, respectively. Furthermore, thermogravimetric analysis (TGA) profiles revealed the enhanced thermal stability of encapsulated biopeptides compared to the free ones. Release kinetic data showed a Fickian diffusion behavior which follows swelling and a diffusion-controlled mechanism for peptides liberation. Finally, as opposed to unloaded MPs, an improvement of the antioxidant activity of the loaded MPs with biopeptides was observed.

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Recently, advances in the synthesis and development of multifunctional nanoparticle platforms have opened up great opportunities and advantages for specifically targeted delivery of genes of interest. BSA-coated niosome structures (NISM@B) can potentially improve the efficiency in vitro delivery of nucleic acid molecules and the transfection of genes. Few studies have reported the combined use of niosomes with nucleic acid as therapeutic agents or decoy oligodeoxynucleotides (ODNs). Herein, we synthesized NISM@B to encapsulate NANOG decoy ODN (NISM@B-DEC), after which the physicochemical characteristics and in vitro and in vivo properties of NISM@B-DEC were investigated. Our results regarding physicochemical characteristics revealed that the stable niosome nanocarrier system was successfully synthesized with a regular spherical shape and narrow size distribution with proper zeta-potential values and had an appropriate biocompatibility. The ODN release from the niosome nanocarrier system exhibited controlled and pH-dependent behavior as the best models to explain the ODN release profile. NISM@B-DEC was efficiently taken up by human glioblastoma cells (U87) and significantly inhibited cell growth. Finally, blockage of the NANOG pathway by NISM@B-DEC resulted in G1 cell cycle arrest, apoptosis, and cell death. In addition, NISM@B-DEC caused a significant decrease in tumor formation and improved wound-healing efficiency of the U87 cells. These findings confirm that NISM@B-DEC could potentially suppress the metastatic ability of these cells. It can be concluded that the presented nanocarrier system can be a promising approach for targeted gene delivery in cancer therapy.

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BACKGROUND: Major cardiac complications have been described in SARS-CoV-2 patients. The study of cardiac troponin' kinetic release is the recommended approach to differentiate acute from chronic injury, in order to clinically manage different cardiac diseases. AIM: To investigate whether serial measurements of high sensitivity troponin I (hs-cTnI) might provide additional information in SARS-CoV-2 patients's clinical management. METHODS: 113 consecutive patients suffering from microbiology proven SARS-CoV2-infection have been studied. Hs-cTnI has been measured in lithium-heparin plasma samples using STAT High Sensitive Troponin I (Architect i2000, Abbott Diagnostics), being 99th percentiles 16 and 34 ng/L for females and males respectively. RESULTS: In 69 out of 113 patients hs-cTnI has been measured, showing in 31 (45%) values higher than 99th percentiles in at least one occasion. In 50 patients (72%) a kinetic evaluation (at least 2 measurements during 24 h) has been carried out. Patients were subdivided into five groups: 1 (n = 44) and 2 (n = 19) no measurement of hs-cTnI or no monitoring respectively; 3 (n = 15) no significant variations during monitoring; 4 (n = 8) and 5 (n = 27) significant variations with values persistently below or sometimes higher than 99th percentiles, respectively. Group 5 patients had a longer hospital stay (median 37 days, p = 0.0001), a more aggressive disease (6 out of 27, 22%, died), more often need admission to ICU (n = 25, 92.6%, p < 0.0001), and show one or more peak values, sometime preceded by severe hypoxia. CONCLUSIONS: In SARS-CoV-2 patients, hs-cTnI serial monitoring may provide additional data to stratify risk, establish prognosis and gaining epidemiological insight on cardiac involvement in this pandemic disease.

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Thymol and silver nanoparticles (Ag-NPs) were used to develop poly(lactic acid) (PLA)-based films with antioxidant and antibacterial performance. Different amounts of thymol (6 and 8 wt%) and 1 wt% Ag-NPs were added to PLA to produce the active films. Ag-NPs and thymol were successfully identified in the nanocomposite structures using spectroscopic techniques. A kinetic study was performed to evaluate the release of thymol and Ag-NPs from the nanocomposites to an aqueous food simulant (ethanol 10%, v/v) at 40 °C. The diffusion of thymol from the polymer matrix was affected by the presence of non-migrating Ag-NPs, which showed non-Fickian release behavior. The ternary system including 1 wt% Ag-NPs and 8 wt% thymol showed clear antibacterial performance by reducing the cell viability of Escherichia coli and Staphylococcus aureus by around 40% after 3 and 24 h of storage at 4, 25, and 37 °C compared to neat PLA. Significant antioxidant behavior of all active films was also confirmed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The obtained nanocomposite films based on PLA and the addition of Ag-NPs and thymol were proven to have combined antioxidant and antibacterial performance, with controlled release of thymol. These formulations have potential applications in the development of innovative and customized active packaging systems to increase the shelf-life of food products.

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This study aimed to develop and characterize the calcium alginate films loaded with diclofenac sodium and other hydrophilic polymers with different degrees of cross-linking obtained by external gelation process. To the formed films different physicochemical evaluation were performed which showed an initial character of the films. The films produced by this external gelation process were found thicker (0.031-0.038 mm) and stronger (51.9-52.9 MPa) but less elastic (2.3%) than those non-cross-linked films (0.029 mm; 39.7 MPa; 4.4%). The lower water vapor permeability (WVP) values of the films were obtained where maximum level of crosslinking occurs. Composite films can be cross-linked in presence of external crosslinking agent to improve the quality of the produced matrices for various uses. The characterization of the film was performed using Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared Spectroscopy (FT-IR) analysis. The Scanning Electron Microscopy (SEM) study showed the morphology of treated composite films. The kinetic release studies showed a sustained release of the drug from the formulated films as it can be prolonged in composite film. The prepared biodegradable Ca-Alginate bio-composite film may be of clinical importance for its therapeutic benefit.

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In this work, we reported the synthesis of curcumin (CUR)-loaded hydrophilic and hydrophobic natural amino acids (AAs)-modified iron oxide magnetic nanoparticles (IONPs). Two types of AAs, l-lysine (Lys) and l-phenylalanine (PhA), were selected to study their effects on loading capacity, release profile of CUR, biocompatibility, and anticancer activity. CUR-loaded AAs-modified IONPs (F@AAs@CUR NPs) were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. Next, the various kinetic equations were fitted to the release data of CUR from F@Lys@CUR NPs and F@PhA@CUR NPs. Additionally, hemolysis test and MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AAs-coated IONPs. Finally, the anticancer activity of F@AAs@CUR NPs examined on MCF-7 breast cancer cell line. The results indicate that these nanocarriers are nontoxic and biocompatible and also F@AAs@CUR NPs are suitable carriers for delivery of curcumin and even other hydrophobic drugs. Also, the MRI training established the effectiveness of IONPs as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity.

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The mobility of arsenic (As) in soil depends on its sorption/desorption processes on soil particles. Plant uptake locally lowers As concentration in soil pore water, which would trigger resupplies of As from soil solid phase. To better understand the fate of As in soil system after its inputs into soil and its subsequent dynamic processes, diffusive gradients in thin films (DGT) technique along with DGT-induced fluxes in soils (DIFS) model were introduced to study the kinetic information of As in soils, including its response time (TC) and resupply rate constant (k-1). To achieve a series of soils with gradient As level, two different types of soils with similar As level (total As in soil JL is 7.4 mg kg-1, while in soil BJ is 6.5 mg kg-1) were collected and amended with exogenous As. Then, DGT deployments were carried out following a period of 90-day soil incubation. The simulated TC values in non-amended soil JL and soil BJ were 0.036 and 0.001 s-1, respectively. The difference may due to the properties of these two soils, including pH values and contents of adsorption materials, such as Fe and Al compounds. After As inputs into soils, the intrinsic rate of As release from the solid phase to the solution phase in As-amended JL soil was much higher than that in non-amended soil. While for soil BJ, a decreasing trend was observed after As spiking. The redistribution of As may responsible for the different variation trends of As kinetics in these two soils after As spiking. The results indicated that the distribution coefficient of As (Kd) in soil was mainly affected by soil Olsen-P content due to an ubiquitous competition between P and As on soil particles.

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Transdermal drug delivery system (TDDS) could be seen as alternative to the oral administration which avoids several adverse effects. In this study a novel TDDS for risedronate (RI), a bisphosphonate used for osteoporosis treatment, based on a vinyl acetate-dioctylfumarate copolymer, poly(VA-co-DOF), previously synthetized, was developed. Two membranes including 6 and 12% (w/w) of drug were obtained, which exhibited good transparence and homogeneous drug distribution, as evaluated by optical microscopy. FTIR spectroscopy and differential scanning calorimetry (DSC) analysis showed no significant drug/polymer interactions, only a plasticizer effect. A new reverse phase high-performance liquid chromatography (RP-HPLC) method for quantification of RI was development and validated, which demonstrate good linearity, reproducibility and accuracy with limits of detection (LOD) and quantification (LOQ) of 0.38µg/mL and 1.17µg/mL, respectively. High drug load efficiency and great drug stability were found. The analysis of the drug release kinetics, fitting to Ritger-Peppas model, leads to values of the diffusion coefficient (n) of 1.37 and 1.05, for 6 and 12% (w/w) RI, respectively. These results correspond to super case transport II and suggest a complex transport mechanism, regulated by the mobility of the polymer chains. Together, these results indicate that this new TDDS could be useful for osteoporosis treatment without adverse effect.

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