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1.
Mol Pharm ; 21(8): 3967-3978, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39018110

ABSTRACT

The metastability of amorphous formulations poses barriers to their safe and widespread commercialization. The propensity of amorphous solid dispersions (ASDs) to crystallize is directly linked to their molecular structure. Amorphous structures are inherently complex and thus difficult to fully characterize by experiments, which makes structural simulations an attractive route for investigating which structural characteristics correlate with ASD stability. In this study, we use empirical potential structure refinement (EPSR) to create molecular models of ketoprofen-poly(vinylpyrrolidone) (KTP/PVP) ASDs with 0-75 wt % drug loading. The EPSR technique uses X-ray total scattering measurements as constraints, yielding models that are consistent with the X-ray data. We perform several simulations to assess the sensitivity of the EPSR approach to input parameters such as intramolecular bond rotations, PVP molecule length, and PVP tacticity. Even at low drug loading (25 wt %), ∼40% of KTP molecules participate in KTP-KTP hydrogen bonding. The extent of KTP-PVP hydrogen bonding does not decrease significantly at higher drug loadings. However, the models' relative uncertainties are too large to conclude whether ASDs' lower stabilities at high drug loadings are due to changes in drug-excipient hydrogen bonding or a decrease in steric hindrance of KTP molecules. This study illustrates how EPSR, combined with total scattering measurements, can be a powerful tool for investigating structural characteristics in amorphous formulations and developing ASDs with improved stability.


Subject(s)
Ketoprofen , Povidone , X-Ray Diffraction , Ketoprofen/chemistry , Povidone/chemistry , X-Ray Diffraction/methods , Crystallization , Chemistry, Pharmaceutical/methods , Drug Compounding/methods , Models, Molecular , Drug Stability
2.
Mol Pharm ; 21(6): 3027-3039, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38755753

ABSTRACT

This study presents a novel approach by utilizing poly(vinylpyrrolidone)s (PVPs) with various topologies as potential matrices for the liquid crystalline (LC) active pharmaceutical ingredient itraconazole (ITZ). We examined amorphous solid dispersions (ASDs) composed of ITZ and (i) self-synthesized linear PVP, (ii) self-synthesized star-shaped PVP, and (iii) commercial linear PVP K30. Differential scanning calorimetry, X-ray diffraction, and broad-band dielectric spectroscopy were employed to get a comprehensive insight into the thermal and structural properties, as well as global and local molecular dynamics of ITZ-PVP systems. The primary objective was to assess the influence of PVPs' topology and the composition of ASD on the LC ordering, changes in the temperature of transitions between mesophases, the rate of their restoration, and finally the solubility of ITZ in the prepared ASDs. Our research clearly showed that regardless of the PVP type, both LC transitions, from smectic (Sm) to nematic (N) and from N to isotropic (I) phases, are effectively suppressed. Moreover, a significant difference in the miscibility of different PVPs with the investigated API was found. This phenomenon also affected the solubility of API, which was the greatest, up to 100 µg/mL in the case of starPVP 85:15 w/w mixture in comparison to neat crystalline API (5 µg/mL). Obtained data emphasize the crucial role of the polymer's topology in designing new pharmaceutical formulations.


Subject(s)
Calorimetry, Differential Scanning , Itraconazole , Liquid Crystals , Povidone , Solubility , X-Ray Diffraction , Itraconazole/chemistry , Liquid Crystals/chemistry , Povidone/chemistry , Calorimetry, Differential Scanning/methods , X-Ray Diffraction/methods , Polymers/chemistry , Antifungal Agents/chemistry , Drug Compounding/methods , Crystallization , Chemistry, Pharmaceutical/methods
3.
Environ Res ; 216(Pt 3): 114706, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36336094

ABSTRACT

Silver nanoparticles (AgNPs) are often used as antibacterial agents. Here, graphene-silver nanoparticles (G-Ag) and graphene-silver nanoparticles poly-vinylpyrrolidone (G-AgPVPy) were prepared by chemical reduction and in-situ polymerization of vinylpyrrolidone (VPy). The prepared G-Ag and G-AgPVPy composites were characterized using various techniques. The size of the AgNPs on the graphene surface in the prepared G-Ag and G-AgPVPy composites was measured as ∼20 nm. The graphene sheets size in the G-Ag and G-AgPVPy composites were measured as 6.0-2.0 µm and 4.0-0.10 µm, respectively, which are much smaller than graphene sheets in graphite powder (GP) (10.0-3.0 µm). The physicochemical analysis confirmed the formation of G-Ag and G-AgPVPy composites and even the distribution of AgNPs and PVPy on the graphene sheets. The synthesized composites (G-AgPVPy, G-Ag) exhibited a broad-spectrum antibacterial potential against both Gram-negative and Gram-positive bacteria. The lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were calculated as >40 µg/mL using G-Ag and GP, while G-AgPVPy showed as 10 µg/mL against Staphylococcus aureus. Among GP, G-Ag, and G-AgPVPy, G-AgPVPy disturbs the cell permeability, damages the cell walls, and causes cell death efficiently. Also, G-AgPVPy was delivered as a significant reusable antibacterial potential candidate. The MIC value (10 µg/mL) did not change up to six subsequent MIC analysis cycles.


Subject(s)
Graphite , Metal Nanoparticles , Graphite/chemistry , Silver/chemistry , Metal Nanoparticles/chemistry , Escherichia coli , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
4.
Mol Pharm ; 18(10): 3882-3893, 2021 10 04.
Article in English | MEDLINE | ID: mdl-34529437

ABSTRACT

Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,ß, a major indicator of the physical stability of neat amorphous pharmaceutical systems.


Subject(s)
Celecoxib/chemistry , Drug Compounding , Drug Stability , Calorimetry, Differential Scanning , Crystallization , Hypromellose Derivatives/chemistry , Povidone/chemistry , Pressure , Pyrrolidines , Spectrum Analysis, Raman , Vinyl Compounds
5.
Macromol Rapid Commun ; 42(16): e2100266, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34173291

ABSTRACT

A versatile one-step synthesis of surface-attached polymer networks using small bifunctional gelators (SBG), namely 4-azidosulfonylphenethyltrimethoxysilane (4-ASPTMS) and 6-azidosulfonylhexyltriethoxysilane (6-ASHTES) is reported. A thin layer (≈200 nm) of a mixture comprising ≈90% precursor polymer and 10% of 4-ASPTMS or 10% 6-ASHTES on a silicon wafer is deposited. Upon UV irradiation (≈l-254 nm) or annealing (>100 °C) layers, sulfonyl azides (SAz) release nitrogen by forming singlet and triplet nitrenes that concurrently react with any C─H bond in the vicinity resulting in sulfonamide crosslinks. Condensation among tri-alkoxy groups (i.e., methoxy or ethoxy) in bulk connects the SBG units, which completes the crosslinking. Concurrently, when such functionalities react with hydroxyl groups at the surface, which enable the covalent attachment of the crosslinked polymer chains. A systematic investigation on reaction mechanism and gel formation using spectroscopic ellipsometry (SE) and Fourier-transform infrared spectroscopy in the attenuated total reflection mode (FTIR-ATR) is performed. Analogous thermally initiated gelation for both 4-ASPTMS and 6-ASHTES is found. The 6-ASHTES is UV inactive at ≈l-254 nm, while the 4-ASPTMS is active and forms gels. The difference is attributed to the aromatic nature of 4-ASPTMS that absorb UV light at ≈l-254 nm due to π-π* transition.


Subject(s)
Polymers , Ultraviolet Rays , Gels , Silicon , Spectroscopy, Fourier Transform Infrared
6.
Mol Pharm ; 17(7): 2703-2720, 2020 07 06.
Article in English | MEDLINE | ID: mdl-32520564

ABSTRACT

A crucial step for the selection of proper amorphous solid dispersion (ASD) matrix carriers is the in-depth assessment of drug/polymer physicochemical properties. In this context, the present study extends the work of previously published attempts by evaluating the formation of simvastatin (SIM)-poly(vinylpyrrolidone) (PVP) ASDs with the aid of thermodynamic and molecular modeling. Specifically, the implementation of both Flory-Huggins lattice theory and molecular dynamics (MD) simulations was able to predict the miscibility between the two components (a finding that was experimentally verified via differential scanning calorimetry (DSC) and hot stage polarized microscopy), while a complete temperature-concentration phase-transition profile was constructed, leading to the identification of the thermodynamically metastable and unstable ASD zones. Furthermore, as in the case of previously published reports, the analysis of the ASDs via Fourier transform infrared spectroscopy did not clarify the type and extent of observed molecular interactions. Hence, in the present study, a computer-based MD simulation model was developed for the first time in order to gain an insight into the properties of the observed interactions. MD amorphous assemblies of SIM, PVP, and their mixtures were initially developed, and the calculated glass transition temperatures were in close agreement with experimentally obtained results, indicating that the developed models could be considered as realistic representations of the actual systems. Furthermore, molecular interactions evaluation via radial distribution function and radius of gyration analysis revealed that increasing SIM content results in a significant PVP chain shrinkage, which eventually leads to SIM-SIM amorphous intermolecular interactions, leading to the formation of amorphous drug zones. Finally, MD-based results were experimentally verified via DSC.


Subject(s)
Molecular Dynamics Simulation , Polymers/chemistry , Povidone/chemistry , Simvastatin/chemistry , Calorimetry, Differential Scanning , Crystallization , Hydrogen Bonding , Phase Transition , Solubility , Thermodynamics , Transition Temperature , X-Ray Diffraction
7.
J Sep Sci ; 43(16): 3285-3293, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32506760

ABSTRACT

Today, wide variety of adsorbents have been developed for sample pretreatment to concentrate and separate harmful substances. However, only a few solid phase microextraction Arrow adsorbents are commercially available. In this study, we developed a new solid phase microextraction Arrow coating, in which nanosheets layered double hydroxides and poly(vinylpyrrolidone) were utilized as the extraction phase and poly(vinyl chloride) as the adhesive. This new coating entailed higher extraction capacity for several volatile organic compounds (allyl methyl sulfide, methyl propyl sulfide, 3-pentanone, 2-butanone, and methyl isobutyl ketone) compared to the commercial Carboxen 1000/polydimethylsiloxane coating. Fabrication parameters for the coating were optimized and extraction and desorption conditions were investigated. The validation of the new solid phase microextraction Arrow coating was accomplished using water sample spiked with volatile organic compounds. Under the optimal conditions, the limits of quantification for the five volatile organic compounds by the new solid phase microextraction Arrow coating and developed gas chromatography with mass spectrometry method were in the range of 0.2-4.6 ng/mL. The proposed method was briefly applied for enrichment of volatile organic compounds in sludge.

8.
Sensors (Basel) ; 20(22)2020 Nov 10.
Article in English | MEDLINE | ID: mdl-33182599

ABSTRACT

Transparent polymer delivery devices often contain a solid lubricant coating on a stronger bulk polymer. The distribution of lubricant coating must be monitored for device optimisation appraisals and to ensure consistency during mass production. However, coating evaluation is difficult to perform as surfaces are often concealed and/or disjointed. Dye stain analysis, which is destructive and time-consuming, is the current industry standard. We present a prototype IR transmission microscope to evaluate micron-level coating coverage of polyurethane and/or polyvinylpyrrolidone on a poly(propylene)-based delivery device. The device has a common industrial configuration, containing a duct and bevel. Inferred absorption of the coating was used to identify coating coverage and a multivariate analysis was used to remove the effects of absorption and scattering by the bulk. Coverage on concealed and disjointed surfaces was imaged and evaluated from a single camera viewpoint and ≈50 µm defects were detectable. The industrial applicability of the prototype was demonstrated using comparisons with dye stain analysis by estimating water dilution of coating and identifying artifacts in coating, which may indicate machine malfunction. The sensitivity and speed of the IR technique makes it a favourable alternative to the current industry standard.

9.
Molecules ; 24(9)2019 May 08.
Article in English | MEDLINE | ID: mdl-31072045

ABSTRACT

A novel sensing system has been designed for the detection of cupric ions. It is based on the quenched fluorescence signal of carbon dots (CDs), which were carbonized from poly(vinylpyrrolidone) (PVP) and L-Cysteine (CYS). Cupric ions interact with the nitrogen and sulfur atoms on surface of the CDs to form an absorbed complex; this results in strong quenching of the fluorescence of the CDs via a fast metal-to-ligand binding affinity. The synthesized water-soluble CDs also exhibited a quantum yield of 7.6%, with favorable photoluminescent properties and good photostability. The fluorescence intensity of the CDs was very stable in high ionic strength (up to 1.0 M NaCl) and over a wide range of pH levels (2.0-12.0). This facile method can therefore develop a sensor that offers reliable, fast, and selective detection of cupric ions with a detection limit down to 0.15 µM and a linear range from 0.5 to 7.0 µM (R2 = 0.980). The CDs were used for cell imaging, observed that they were low toxicity to Tramp C1 cells and exhibited blue and green and red fluorescence under a fluorescence microscope. In summary, the CDs exhibited excellent fluorescence properties, and could be applied to the selective and sensitive detection of cupric ion and multicolor cell imaging.


Subject(s)
Carbon/chemistry , Copper/analysis , Imaging, Three-Dimensional/methods , Molecular Probes/chemical synthesis , Quantum Dots/chemistry , Animals , Carbon/toxicity , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Fluorescence , Ions , Mice, Transgenic , Molecular Probes/chemistry , Photoelectron Spectroscopy , Quantum Dots/toxicity , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/analysis
10.
J Biomater Sci Polym Ed ; 35(11): 1706-1725, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38754029

ABSTRACT

Biopolymers have the utmost significance in biomedical applications and blending synthetic polymers has shown favorable characteristics versus individual counterparts. The utilization of the blends can be restricted through the use of toxic chemical agents such as initiators or crosslinkers. In this regard, a chemical agent-free ionizing irradiation is a beneficial alternative for preparing the hydrogels for biomedical applications. In this study, carboxymethyl chitosan (CM-CS), guar gum (GG), and poly(vinylpyrrolidone) (PVP) based ternary blends (TB) were crosslinked using various doses of ionizing irradiation to fabricate hydrogels. The prepared hydrogels were characterized for physicochemical properties, swelling analysis, biological assays, and drug delivery applications. Swelling analysis in distilled water revealed that the hydrogels exhibit excellent swelling characteristics. An in vitro cytocompatibility assay showed that the hydrogels have greater than 90% cell viability for the human epithelial cell line and a decreasing cell viability trend for the human alveolar adenocarcinoma cell line. In addition, the prepared hydrogels possessed excellent antibacterial characteristics against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). Finally, the release studies of anti-inflammatory Quercus acutissima (QA) loaded hydrogels exhibited more than 80% release in phosphate-buffered saline (pH = 7.4). These findings suggest that TB hydrogels can be used as suitable carrier media for different release systems and biomedical applications.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Cell Survival , Chitosan , Escherichia coli , Galactans , Hydrogels , Mannans , Plant Gums , Povidone , Staphylococcus aureus , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/chemical synthesis , Chitosan/pharmacology , Plant Gums/chemistry , Galactans/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Hydrogels/pharmacology , Mannans/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Humans , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Povidone/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Liberation , A549 Cells
11.
Sci Total Environ ; 916: 170320, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38278278

ABSTRACT

In environmental analysis, the detection of water-soluble synthetic polymers (WSSP) presents considerable challenges. Thus, a precise and reproducible analytical method was developed using continuous-flow off-line pyrolysis with gas chromatography/mass spectrometry (GC/MS) to simultaneously identify multiple water-soluble polymers from a single environmental sample. WSSP are widely used in multiple industries as hydrogels due to their hydrophilic character and potential biocompatibility. This adaptability of hydrogels is reflected in their ability to provide customized formulations for specific needs, such as in the development of personal care products, medicine, and pharmaceuticals. Specifically, polyvinylpyrrolidone (PVP), poly(N-vinylcaprolactam) (PNVCL), and polyethyleneimine (PEI) were targeted for analysis in wastewater, employing unique pyrolysis products for identification. These polymers require careful assessment in wastewater to evaluate potential environmental risks associated with their release. PVP and PNVCL were identified through two pyrolysis products, while six pyrolysis products were utilized for the identification of PEI. The validated method demonstrated very good linearity and reproducibility, with correlation coefficients ranging from 0.94 to 0.99 and relative standard deviation (RSD) values between 3 % and 36 % for the targeted compounds. The limit of quantification (LOQ) for the three polymers ranged from 1 to 10 µg L-1. Moreover, the average recovery rates for these polymers, determined from artificial water samples, were approx. 85 %. Utilizing the validated method, water samples from seven wastewater treatment plants in Germany were successfully analyzed, confirming the presence of these polymers at elevated concentrations in the µg L-1 range. Notably, untreated influent waters exhibited higher polymer levels compared to treated influents and effluents, underscoring their significant contribution to overall polymer content. The developed analytical method provides an efficient tool for the simultaneous identification and quantification of PVP, PNVCL, and PEI in wastewater samples. The results highlighted the prevalent presence of PVP, PNVCL, and PEI in the tested wastewater samples, indicating their significant abundance.

12.
J Pharm Sci ; 112(9): 2444-2452, 2023 09.
Article in English | MEDLINE | ID: mdl-36965843

ABSTRACT

Amorphous solid dispersions (ASDs) are one of the promising strategies to improve the solubility and dissolution rate of poorly soluble compounds. In this study, Molecular Dynamics simulations were used to investigate the interactions between three selected stilbenoids with important biological activity (resveratrol, pinostilbene and pterostilbene) and poly(vinylpyrrolidone). The analysis of the pair distribution functions and hydrogen bond distributions reveals a significant weakening of the hydrogen bond network of the stilbenoids in ASDs compared to the pure (no polymer) amorphous systems. This is accompanied by an increase in the mobility of the stilbenoid molecules in the ASDs, both in the translational dynamics determined from the molecular mean square displacements, and in the molecular reorientations followed by analysing several torsional distributions.


Subject(s)
Molecular Dynamics Simulation , Stilbenes , Polymers/chemistry , Solubility
13.
ACS Appl Mater Interfaces ; 15(33): 39027-39038, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37581368

ABSTRACT

Design criteria for controlling engineered nanomaterial (ENM) antimicrobial performance will enable advances in medical, food production, processing and preservation, and water treatment applications. In pursuit of this goal, better resolution of how specific ENM properties, such as nanoparticle shape, influence antimicrobial activity is needed. This study probes the antimicrobial activity toward a model Gram-negative bacterium, Escherichia coli (E. coli), that results from interfacial interactions with differently shaped silver nanoparticles (AgNPs): cube-, disc-, and pseudospherical-AgNPs. The EC50 value (i.e., the concentration of AgNPs that inactivates 50% of the microbial population) for each shape is identified and presented as a function of mass, surface area, and particle number. Further, shifts in relative potency are identified from the associated dose-response curves (e.g., shifts left, to lower concentrations, indicate greater potency). When using a mass-based dose metric, the disc-AgNPs present the highest antimicrobial activity of the three shapes (EC50: 2.39 ± 0.26 µg/mL for discs, 2.99 ± 0.96 µg/mL for cubes, 116.33 ± 6.43 µg/mL for pseudospheres). When surface area and particle number are used as dose metrics, the cube-AgNPs possess the highest antimicrobial activity (EC50-surface area: 4.70 × 10-5 ± 1.51 × 10-5 m2/mL, EC50-particle: 5.97 × 109 ± 1.92 × 109 particles/mL), such that the relative trend in potency becomes cubes > discs > pseudospheres and cubes ≫ discs ⩾ pseudospheres, respectively. The results reveal that the antimicrobial potency of disc-AgNPs is sensitive to the dose metric, significantly decreasing in potency (∼5-30×) upon conversion from a mass-based concentration to surface area and particle number and influencing the conclusions drawn. The shift in relative particle potency highlights the importance of investigating various dose metrics within the experimental design and signals different particle parameters influencing shape-based antimicrobial activity. To probe shape-dependent behavior, we use a unique empirical approach where the physical and chemical properties (ligand chemistry, surface charge) of the AgNP shapes are carefully controlled, and total available surface area is equivalent across shapes as made through modifications to particle size and concentration. The results herein suggest that surface area alone does not drive antimicrobial activity as the different AgNP shapes at equivalent particle surface area yield significantly different magnitudes of antimicrobial activity (i.e., 100% inactivation for cube-AgNPs, <25% inactivation for disc- and pseudospherical-AgNPs). Further, the particle shapes studied possess different crystal facets, illuminating their potential influence on differentiating interactions between the particle surface and the microbe. Whereas surface area may partly contribute to antimicrobial activity in certain ENM shapes (i.e., disc-AgNPs in relation to the pseudospherical-AgNPs), the different magnitudes of antimicrobial activity across shape provide insight into the likely role of other particle-specific factors, such as crystal facets, driving the antimicrobial activity of other shapes (i.e., cube-AgNPs).


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Metal Nanoparticles/chemistry , Escherichia coli , Silver/pharmacology , Silver/chemistry , Anti-Infective Agents/chemistry , Bacteria , Particle Size , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests
14.
Polymers (Basel) ; 14(21)2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36365697

ABSTRACT

Owing to their suitable physical and chemical properties, hydrogels have been considered a convenient choice for wound dressings because of the advantages that they offer, such as maintaining the moist environment required for wound healing. In this research, interpenetrating hydrogels of polyphenol-functionalized gelatin (GE), a water-soluble protein derived from natural polymer collagen with excellent biocompatibility, no immunogenicity, and hydrophilicity, and polyvinylpyrrolidone (PVP), a hydrophilic, non-toxic, biodegradable, biocompatible polymer that is soluble in many solvents, widely used in biomedical applications, particularly as a basic material for the manufacturing of hydrogel wound dressings, were synthesized. Gallic acid (GA) was selected in this work to study whether the interpenetrating polymer networks (IPNs) synthesized can provide antioxidant properties given that this material is intended to be used as a potential wound dressing. The obtained IPN hydrogels showed improved mechanical properties in comparison with pristine gelatin network (net-GE), a porous structure, and good thermal stability for biological applications. The antioxidant capacity of the IPNs functionalized with GA was compared to Trolox standards, obtaining a radical scavenging activity (RSA%) equivalent to a Trolox concentration of 400 µM.

15.
ACS Appl Bio Mater ; 5(6): 2880-2893, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35583459

ABSTRACT

Malva sylvestris (MS) is a medicinal herb known worldwide for its beneficial effects due to the several active molecules present in its leaves and flowers. These compounds have shown antioxidant and anti-inflammatory properties and thus can be helpful in treatments of burns and chronic wounds, characterized mainly by high levels of free radicals and impairments of the inflammatory response. In this work, we propose bilayer films as wound dressings, based on poly(vinylpyrrolidone) (PVP) and sodium alginate loaded with M. sylvestris extracts from leaves and flowers and fabricated by combining solvent-casting and rod-coating methods. The top layer is produced in two different PVP/alginate ratios and loaded with the MS flowers' extract, while the bottom layer is composed of PVP and MS leaves' extract. The bilayers were characterized morphologically, chemically, and mechanically, while they showed superior self-adhesive properties on human skin compared to a commercial skin patch. The materials showed antioxidant activity, release of the bioactive compounds, and water uptake property. Moreover, the anthocyanin content of the flower extract provided the films with the ability to change color when immersed in buffers of different pH levels. In vitro tests using primary keratinocytes demonstrated the biocompatibility of the MS bilayer materials and their capacity to enhance the proliferation of the cells in a wound scratch model. Finally, the best performing MS bilayer sample with a PVP/alginate ratio of 70:30 was evaluated in mice models, showing suitable resorption properties and the capacity to reduce the level of inflammatory mediators in UVB-induced burns when applied to an open wound. These outcomes suggest that the fabricated bilayer films loaded with M. sylvestris extracts are promising formulations as active and multifunctional dressings for treating skin disorders.


Subject(s)
Burns , Malva , Adhesives , Alginates , Animals , Antioxidants/pharmacology , Bandages , Malva/chemistry , Mice , Plant Extracts/pharmacology , Resin Cements
16.
Nanomaterials (Basel) ; 12(18)2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36144968

ABSTRACT

In the present study, we report on the successful synthesis of hollow iron oxide nanospheres. The hollow Fe3O4 nanospheres were synthesized following a four-step procedure: electrospraying spherical PVP particles, coating these particles with alumina (Al2O3) and hematite (Fe2O3) through atomic layer deposition and, finally, a thermal reduction process to degrade the polymer (PVP) and convert hematite (Fe2O3) into magnetite (Fe3O4). A structural analysis using X-ray diffraction (XRD) confirmed the effectiveness of the thermal reduction process. A morphological analysis confirmed that the four-step procedure allowed for the obtainment of hollow iron oxide nanospheres, even though the reduction process caused a contraction in the diameter of the particles of almost 300 nm, but did not affect the thickness of the walls of the hollow spheres that remained at approximately 15 nm. Magnetic properties of the hollow iron oxide nanospheres enable their use in applications where the agglomeration of magnetic nanostructures in liquid media is commonly not allowed, such as in drug encapsulation and delivery.

17.
Drug Deliv Transl Res ; 12(4): 931-943, 2022 04.
Article in English | MEDLINE | ID: mdl-34302273

ABSTRACT

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)-based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays' reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.


Subject(s)
Amphotericin B , Eye Infections, Fungal , Humans , Administration, Cutaneous , Drug Delivery Systems/methods , Eye Infections, Fungal/drug therapy , Hyaluronic Acid/therapeutic use , Needles , Reproducibility of Results
18.
ACS Appl Mater Interfaces ; 13(46): 55489-55497, 2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34761893

ABSTRACT

The instability of van der Waals (vdW) materials leads to spontaneous morphological and chemical transformations in the air. Although the passivation of vdW materials with other resistive materials is often used to solve stability issues, this passivation layer can block carrier injection and thus interfere with charge transfer doping. In this study, a facile method is proposed for n-doping and mediation of Se vacancies in tungsten diselenide (WSe2) by poly(vinylpyrrolidone) (PVP) coating. The major carrier type of the PVP-coated WSe2-based field-effect transistor (FET) was converted from hole (p-type) to electron (n-type). Furthermore, the vacancy-induced interface trap density was reduced by approximately 500 times. This study provides a practical doping and passivation method for the van der Waals materials, as well as a comprehensive understanding of the chemical reaction and electronic transport in these materials.

19.
Materials (Basel) ; 14(21)2021 Nov 03.
Article in English | MEDLINE | ID: mdl-34772151

ABSTRACT

The current paper presents a strategic way to design and develop materials with properties adapted for various applications from biomedicine to environmental applications. In this context, blends of (hydroxypropyl)methyl cellulose (HPMC) and poly(vinylpyrrolidone) (PVP) were obtained to create new materials that can modulate the membrane properties in various fields. Thus, to explore the possibility of using the HPMC/PVP system in practical applications, the solubility parameters in various solvents were initially evaluated using experimental and theoretical approaches. In this frame, the study is aimed at presenting the background and steps of preliminary studies to validate the blends behavior for targeted application before being designed. Subsequently, the analysis of the behavior in aqueous dilute solution of HPMC/PVP blend offers information about the conformational modifications and interactions manifested in system depending on the structural characteristics of polymers (hydrophilicity, flexibility), polymer mixtures composition, and used solvent. Given this background, based on experimental and theoretical studies, knowledge of hydrodynamic parameters and analysis of the optimal compositions of polymer mixtures are essential for establishing the behavior of obtained materials and validation for most suitable applications. Additionally, to guarantee the quality and functionality of these composite materials in the targeted applications, e.g., biomedical or environmental, the choice of a suitable solvent played an important role.

20.
Carbohydr Polym ; 258: 117718, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33593580

ABSTRACT

Herein, carboxymethyl chitosan and poly(vinylpyrrolidone) based hydrogels were synthesized by electron beam irradiation with dose variations (15 kGy, 30 kGy, and 45 kGy) for drug delivery applications. Irradiation crosslinked hydrogels were characterized for swellings in different medias, chemical, thermal, cell cytotoxicity, and drug release aspects. Swelling analysis was evaluated in distilled water, buffer, and saline solutions. Fourier transform infrared analysis revealed the establishment of physical interactions and confirmed the presence of functional groups present in the drug carriers. Scanning electron microscopy depicted the porous structure, which is responsible for swelling, drug loading, and release. Cell cytotoxicity assays indicated good cell viability on RAW 264.7 cells and anticancer activity on cancerous AGS cell lines. Cumulative drug release (%) of kanamycin in PBS at pH 7.4 was more than 90 % at 168 h. These drug carriers show promise to be developed as a sustained drug delivery system.


Subject(s)
Antineoplastic Agents/administration & dosage , Chitosan/analogs & derivatives , Drug Carriers , Drug Delivery Systems , Hydrogels/chemistry , Kanamycin/administration & dosage , Povidone/chemistry , Animals , Cell Line, Tumor , Cell Survival , Chitosan/chemistry , Cross-Linking Reagents/chemistry , Delayed-Action Preparations , Diffusion , Drug Liberation , Electrons , Hydrogen-Ion Concentration , In Vitro Techniques , Kanamycin/pharmacology , Mice , Microscopy, Electron, Scanning , Porosity , RAW 264.7 Cells , Spectroscopy, Fourier Transform Infrared
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