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1.
Anal Chem ; 94(8): 3427-3431, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35156816

RESUMEN

Hydrazone-based molecular switches serve as efficient ratiometric pH-sensitive agents that can be tracked with 19F NMR/MRI and 1H NMR. Structural changes induced between pH 3 and 4 lead to signal appearance and disappearance at 1H and 19F NMR spectra allowing ratiometric pH measurements. The most pronounced are resonances of the CF3 group shifted by 1.8 ppm with 19F NMR and a hydrazone proton shifted by 2 ppm with 1H NMR.


Asunto(s)
Medios de Contraste , Hidrazonas , Medios de Contraste/química , Hidrazonas/química , Concentración de Iones de Hidrógeno , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética
2.
Int J Mol Sci ; 22(23)2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34884566

RESUMEN

Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug's toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80-200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).


Asunto(s)
Aminoácidos/química , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Fluorouracilo/farmacología , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Nanopartículas/administración & dosificación , Animales , Antimetabolitos Antineoplásicos/química , Antimetabolitos Antineoplásicos/farmacología , Femenino , Fluorouracilo/química , Neoplasias Mamarias Experimentales/patología , Nanopartículas/química , Células Tumorales Cultivadas
3.
AAPS PharmSciTech ; 22(3): 109, 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33718994

RESUMEN

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.


Asunto(s)
Criogeles/síntesis química , Alcohol Polivinílico/síntesis química , Resveratrol/síntesis química , Cicatrización de Heridas , Antioxidantes/administración & dosificación , Antioxidantes/síntesis química , Antioxidantes/farmacocinética , Vendas Hidrocoloidales , Criogeles/administración & dosificación , Criogeles/farmacocinética , Alcohol Polivinílico/administración & dosificación , Alcohol Polivinílico/farmacocinética , Resveratrol/administración & dosificación , Resveratrol/farmacocinética , Resistencia a la Tracción/efectos de los fármacos , Resistencia a la Tracción/fisiología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología
4.
NMR Biomed ; 33(7): e4306, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32253803

RESUMEN

PURPOSE: Although anorexia nervosa is classified as a psychiatric disorder associated with socio-environmental and psychological factors, a deeper insight into the dominant neurobiological basis is needed to develop a more effective approach of treatment. Given the high contribution of genetic predisposition and the underlying pathophysiology of neurohormonal circuits, it seems that pharmacological targeting of these mechanisms may provide us with better therapeutic outcomes. METHODS: 1 H-NMR spectroscopy was used to measure concentrations of the hypothalamus and brain stem metabolites in an activity-based rodent model (ABA) after subcutaneous administration of kisspeptin-10. Because anorexia mainly affects young women and often leads to hypogonadotropic-hypogonadism, we investigated the influence of this neuropeptide, which is involved in reproductive function by regulating the hypothalamic-pituitary-gonadal axis, on the ABA model development. RESULTS: Kisspeptin reinforced food consumption in an activity-based rodent model of anorexia changing a pattern of weight loss. 1 H-NMR spectroscopy of the hypothalamus and brain stem of ABA rats revealed a statistically significant change in the concentration of creatine (Cr; decreased, P = 0.030), phosphocreatine (PCr; increased, P = 0.030), γ-aminobutyric acid (GABA; decreased, P = 0.011), glutathione (GSH; increased, P = 0.011) and inositol (INS; increased, P = 0.047) compared to the control group. Subcutaneous administration of kisspeptin reversed the decrease in GABA (P = 0.018) and Cr (P = 0.030) levels in the hypothalamus as well as restored glutamate (GLU; P = 0.040) level in the brain stem. CONCLUSIONS: We suspect that kisspeptin through modulation of hypothalamic GABAergic signaling increases food intake, and thus positively alters brain metabolism.


Asunto(s)
Anorexia/metabolismo , Tronco Encefálico/química , Hipotálamo/química , Kisspeptinas/administración & dosificación , Kisspeptinas/farmacología , Animales , Peso Corporal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Hipotálamo/efectos de los fármacos , Metaboloma/efectos de los fármacos , Espectroscopía de Protones por Resonancia Magnética , Ratas Wistar
5.
Langmuir ; 36(32): 9534-9539, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32706252

RESUMEN

The aim of our study was to develop a novel method for nanocarriers' preparation as a fluorine magnetic resonance imaging (19F MRI)-detectable drug delivery system. The novelty of the proposed approach is based on the application of fluorinated polyelectrolyte Nafion as a contrast agent since typical MRI contrast agents are based on paramagnetic gadolinium or ferro/superparamagnetic iron oxide compounds. An advantage of using an 19F-based tracer comes from the fact that the 19F image is detected at a different resonance frequency than the 1H image. In addition, the close to zero natural concentration of 19F nuclei in the human body makes fluorine atoms a promising MRI marker without any natural background signal. That creates the opportunity to localize and identify only exogenous fluorinated compounds with 100% specificity. The nanocarriers were formed by the deposition of polyelectrolytes on nanoemulsion droplets via the layer-by-layer technique with the saturation approach. The polyelectrolyte multilayer shell was composed of Nafion, the fluorinated ionic polymer used for labeling by 19F nuclei, and poly-l-lysine (PLL). The surface of such prepared nanocarriers was further pegylated by adsorption of pegylated polyanion, poly-l-glutamic acid (PGA). The 19F MRI-detectable hydrophobic nanocarriers with an average size of 170 nm and a sufficient signal-to-noise ratio have been developed and optimized to be used for passive tumor targeting and drug delivery.

6.
Pharm Res ; 35(7): 144, 2018 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-29777389

RESUMEN

PURPOSE: The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety. METHODS: Fe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction. Magnetic resonance relaxometry and MRI were carried out on phantoms of the MOF system suspended in polymer solution. Drug dissolution studies were conducted using Franz cells. For MOF cytotoxicity, commercially available fibroblasts L929 were cultured in Eagle's Minimum Essential Medium supplemented with 10% fetal bovine serum. RESULTS: MOF particles were loaded with 12% of isoniazid. The particle size (3.37-6.45 µm) depended on the micronization method used. The proposed drug delivery system can also serve as the MRI contrast agent. The drug dissolution showed extended release of isoniazid. MOF particles accumulated in the L929 fibroblast cytoplasmic area, suggesting MOF release the drug inside the cells. The cytotoxicity confirmed safety of MOF system. CONCLUSIONS: The application of MOF for extended release inhalable system proposes the novel strategy for delivery of standard antimycobacterial agents combined with monitoring of their distribution within the lung tissue.


Asunto(s)
Antituberculosos/química , Portadores de Fármacos/química , Hierro/química , Nanomedicina Teranóstica/métodos , Tuberculosis , Animales , Antituberculosos/administración & dosificación , Antituberculosos/metabolismo , Línea Celular , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Hierro/administración & dosificación , Hierro/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Tuberculosis/tratamiento farmacológico , Tuberculosis/metabolismo
7.
AAPS PharmSciTech ; 17(3): 735-42, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26335419

RESUMEN

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.


Asunto(s)
Liberación de Fármacos , Derivados de la Hipromelosa/química , Derivados de la Hipromelosa/farmacocinética , Fumarato de Quetiapina/química , Fumarato de Quetiapina/farmacocinética , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Solubilidad , Comprimidos
8.
Pharm Res ; 31(9): 2383-92, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24633415

RESUMEN

PURPOSE: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. METHODS: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. RESULTS: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. CONCLUSIONS: We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.


Asunto(s)
Preparaciones de Acción Retardada/análisis , Derivados de la Hipromelosa/análisis , Imagen por Resonancia Magnética/métodos , Microscopía/métodos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/química , Cetoprofeno/administración & dosificación , Cetoprofeno/química , Levodopa/administración & dosificación , Levodopa/química , Solubilidad , Comprimidos
9.
BMC Med Imaging ; 13: 20, 2013 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-23865826

RESUMEN

BACKGROUND: Standard MRI has been used for high-grade gliomas detection, albeit with limited success as it does not provide sufficient specificity and sensitivity to detect complex tumor structure. Therefore targeted contrast agents based on iron oxide, that shorten mostly T2 relaxation time, have been recently applied. However pulse sequences for molecular imaging in animal models of gliomas have not been yet fully studied. The aim of this study was therefore to compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular MRI of glioma. METHODS: A mouse model was used. U87MGdEGFRvIII cells (U87MG), derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was used and MR imaging was performed on the 10 day after the inoculation of the tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI, GE and GEFC pulse sequences. RESULTS: The results showed significant differences in CNR among all pulse sequences prior injection. GEFC provided higher CNR post contrast agent injection when compared to GE and SE. Post injection CNR was the highest with SWI and significantly different from any other pulse sequence. CONCLUSIONS: Molecular MR imaging using targeted contrast agents can enhance the detection of glioma cells at 9.4 T if the optimal pulse sequence is used. Hence, the use of flow compensated pulse sequences, beside SWI, should to be considered in the molecular imaging studies.


Asunto(s)
Medios de Contraste , Glioma/patología , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita , Animales , Línea Celular Tumoral , Glioma/diagnóstico , Humanos , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Experimentales , Flujo Pulsátil
10.
Nanomaterials (Basel) ; 13(15)2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37570481

RESUMEN

Poor pharmacokinetics and low aqueous solubility combined with rapid clearance from the circulation of drugs result in their limited effectiveness and generally high therapeutic doses. The use of nanocarriers for drug delivery can prevent the rapid degradation of the drug, leading to its increased half-life. It can also improve the solubility and stability of drugs, advance their distribution and targeting, ensure a sustained release, and reduce drug resistance by delivering multiple therapeutic agents simultaneously. Furthermore, nanotechnology enables the combination of therapeutics with biomedical imaging agents and other treatment modalities to overcome the challenges of disease diagnosis and therapy. Such an approach is referred to as "theranostics" and aims to offer a more patient-specific approach through the observation of the distribution of contrast agents that are linked to therapeutics. The purpose of this paper is to present the recent scientific reports on polymeric nanocarriers for MRI-guided drug delivery. Polymeric nanocarriers are a very broad and versatile group of materials for drug delivery, providing high loading capacities, improved pharmacokinetics, and biocompatibility. The main focus was on the contrasting properties of proposed polymeric nanocarriers, which can be categorized into three main groups: polymeric nanocarriers (1) with relaxation-type contrast agents, (2) with chemical exchange saturation transfer (CEST) properties, and (3) with direct detection contrast agents based on fluorinated compounds. The importance of this aspect tends to be downplayed, despite its being essential for the successful design of applicable theranostic nanocarriers for image-guided drug delivery. If available, cytotoxicity and therapeutic effects were also summarized.

11.
ACS Sens ; 8(5): 1971-1979, 2023 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-37198734

RESUMEN

The design and synthesis of hydrazone-based switches with a CF3 reporting group for 19F pH imaging using relaxation rate changes were described. A paramagnetic center was introduced into the hydrazone molecular switch scaffold by substitution of an ethyl functional group with a paramagnetic complex. The mechanism of activation relies on a gradual increase in T1 and T2 magnetic resonance imaging (MRI) relaxation times as pH decreases due to E/Z isomerization, which results in a change in the distance between fluorine atoms and the paramagnetic center. Among the three possible variants of the ligand, the meta isomer was found to offer the highest potential changes in relaxation rates due to the significant paramagnetic relaxation enhancement (PRE) effect and a stable position of the 19F signal, allowing for the tracking of a single narrow 19F resonance for imaging purposes. The selection of the most suitable Gd(III) paramagnetic ion for complexation was conducted by theoretical calculations based on the Bloch-Redfield-Wangsness (BRW) theory, taking into account the electron-nucleus dipole-dipole and Curie interactions only. The results were verified experimentally, confirming the accuracy of theoretical predictions, good solubility, and stability of the agents in water and the reversible transition between E and Z-H+ isomers. The results demonstrate the potential of this approach for pH imaging using relaxation rate changes instead of chemical shift.


Asunto(s)
Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Concentración de Iones de Hidrógeno
12.
Acta Biomater ; 166: 360-374, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37172636

RESUMEN

Tendon fascicle bundles are often used as biological grafts and thus must meet certain quality requirements, such as excluding calcification, which alters the biomechanical properties of soft tissues. In this work, we investigate the influence of early-stage calcification on the mechanical and structural properties of tendon fascicle bundles with varying matrix content. The calcification process was modeled using sample incubation in concentrated simulated body fluid. Mechanical and structural properties were investigated using uniaxial tests with relaxation periods, dynamic mechanical analysis, as well as magnetic resonance imaging and atomic force microscopy. Mechanical tests showed that the initial phase of calcification causes an increase in the elasticity, storage, and loss modulus, as well as a drop in the normalized value of hysteresis. Further calcification of the samples results in decreased modulus of elasticity and a slight increase in the normalized value of hysteresis. Analysis via MRI and scanning electron microscopy showed that incubation alters fibrillar relationships within the tendon structure and the flow of body fluids. In the initial stage of calcification, calcium phosphate crystals are barely visible; however, extending the incubation time for the next 14 days results in the appearance of calcium phosphate crystals within the tendon structure and leads to damage in its structure. Our results show that the calcification process modifies the collagen-matrix relationships and leads to a change in their mechanical properties. These findings will help to understand the pathogenesis of clinical conditions caused by calcification process, leading to the development of effective treatments for these conditions. STATEMENT OF SIGNIFICANCE: This study investigates how calcium mineral deposition in tendons affects their mechanical response and which processes are responsible for this phenomenon. By analyzing the elastic and viscoelastic properties of animal fascicle bundles affected by calcification induced via incubation in concentrated simulated body fluid, the study sheds light on the relationship between structural and biochemical changes in tendons and their altered mechanical response. This understanding is crucial for optimizing tendinopathy treatment and preventing tendon injury. The findings provide insights into the calcification pathway and its resulting changes in the biomechanical behaviors of affected tendons, which have been previously unclear.


Asunto(s)
Calcinosis , Tendones , Animales , Fenómenos Biomecánicos , Tendones/fisiología , Colágeno , Fosfatos de Calcio
13.
Pharm Res ; 29(12): 3420-33, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22923349

RESUMEN

PURPOSE: To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. METHODS: Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. RESULTS: Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. CONCLUSIONS: The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Metilcelulosa/análogos & derivados , Agua/química , Derivados de la Hipromelosa , Metilcelulosa/química , Microscopía/métodos , Comprimidos/química
14.
Pharm Res ; 28(5): 1065-73, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21181545

RESUMEN

PURPOSE: The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. METHODS: A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow-through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmentation algorithms due to trimodal structure of the image intensity histograms. RESULTS: Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. CONCLUSIONS: The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/FTIR studies.


Asunto(s)
Lactosa/análogos & derivados , Imagen por Resonancia Magnética/métodos , Metilcelulosa/análogos & derivados , Preparaciones Farmacéuticas/química , Lactosa/química , Imagen por Resonancia Magnética/instrumentación , Metilcelulosa/química , Solubilidad , Comprimidos/química
15.
Mater Sci Eng C Mater Biol Appl ; 130: 112435, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34702520

RESUMEN

In this work, we investigate differences in the mechanical and structural properties of tendon fascicle bundles dissected from different areas of bovine tendons. The properties of tendon fascicle bundles were investigated by means of uniaxial tests with relaxation periods and hysteresis, dynamic mechanical analysis (DMA), as well as magnetic resonance imaging (MRI). Uniaxial tests with relaxation periods revealed greater elastic modulus, hysteresis, as well as stress drop during the relaxation of samples dissected from the posterior side of the tendon. However, the normalized stress relaxation curves did not show a statistically significant difference in the stress drop between specimens cut from different zones or between different strain levels. Using dynamic mechanical analysis, we found that fascicle bundles dissected from the anterior side of the tendon had lower storage and loss moduli, which could result from altered fluid flow within the interfascicular matrix (IFM). The lower water content, diffusivity, and higher fractional anisotropy of the posterior part of the tendon, as observed using MRI, indicates a different structure of the IFM, which controls the flow of fluids within the tendon. Our results show that the viscoelastic response to dynamic loading is correlated with fluid flow within the IFM, which was confirmed during analysis of the MRI results. In contrast to this, the long-term relaxation of tendon fascicle bundles is controlled by viscoplasticity of the IFM and depends on the spatial distribution of the matrix within the tendon. Comparison of results from tensile tests, DMA, and MRI gives new insight into tendon mechanics and the role of the IFM. These findings may be useful in improving the diagnosis of tendon injury and effectiveness of medical treatments for tendinopathies.


Asunto(s)
Líquidos Corporales , Tejido Nervioso , Tendinopatía , Animales , Bovinos , Módulo de Elasticidad , Estrés Mecánico , Tendones/diagnóstico por imagen
16.
Materials (Basel) ; 14(24)2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34947294

RESUMEN

Wound dressings when applied are in contact with wound exudates in vivo or with acceptor fluid when testing drug release from wound dressing in vitro. Therefore, the assessment of bidirectional mass transport phenomena in dressing after application on the substrate is important but has never been addressed in this context. For this reason, an in vitro wound dressing stack model was developed and implemented in the 3D printed holder. The stack was imaged using magnetic resonance imaging, i.e., relaxometric imaging was performed by means of T2 relaxation time and signal amplitude 1D profiles across the wound stack. As a substrate, fetal bovine serum or propylene glycol were used to simulate in vivo or in vitro cases. Multi-exponential analysis of the spatially resolved magnetic resonance signal enabled to distinguish components originating from water and propylene glycol in various environments. The spatiotemporal evolution of these components was assessed. The components were related to mass transport (water, propylene glycol) in the dressing/substrate system and subsequent changes of physicochemical properties of the dressing and adjacent substrate. Sharp changes in spatial profiles were detected and identified as moving fronts. It can be concluded that: (1) An attempt to assess mass transport phenomena was carried out revealing the spatial structure of the wound dressing in terms of moving fronts and corresponding layers; (2) Moving fronts, layers and their temporal evolution originated from bidirectional mass transport between wound dressing and substrate. The setup can be further applied to dressings containing drugs.

17.
Materials (Basel) ; 14(21)2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34772056

RESUMEN

The purpose was to show, using destructive/nondestructive methods, that the interplay between water, tablet structure, and composition determine the unique spatiotemporal hydration pattern of polymer-based matrices. The tablets containing a 1:1 w/w mixture of sodium alginate with salicylic acid (ALG/SA) or sodium salicylate (ALG/SNA) were studied using Karl Fischer titration, differential scanning calorimetry, X-ray microtomography, and magnetic resonance imaging. As the principal results, matrix specific features were detected, e.g., "locking" of the internal part of the matrix (ALG/SA); existence of lamellar region associated with detection of free/freezing water (ALG/SA); existence of water penetrating the matrix forming specific region preceding infiltration layer (ALG/SNA); switch in the onset temperature of endothermic water peak associated with an increase in the fraction of non-freezing water weight per dry matrix weight in the infiltration layer (ALG/SNA). The existence of complicated spatiotemporal hydration patterns influenced by matrix composition and molecular properties of constituents has been demonstrated.

18.
Int J Nanomedicine ; 16: 1377-1390, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658778

RESUMEN

BACKGROUND: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. METHODS: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. RESULTS: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. CONCLUSION: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.


Asunto(s)
Curcumina/administración & dosificación , Curcumina/uso terapéutico , Ácido Hialurónico/química , Hipertensión/tratamiento farmacológico , Nanocápsulas/química , Administración Oral , Animales , Aorta/efectos de los fármacos , Aorta/patología , Presión Sanguínea/efectos de los fármacos , Curcumina/farmacología , Diástole/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flúor/química , Frecuencia Cardíaca/efectos de los fármacos , Hidrodinámica , Interacciones Hidrofóbicas e Hidrofílicas , Hipertensión/fisiopatología , Espectroscopía de Resonancia Magnética , Masculino , Tamaño de la Partícula , Ratas , Electricidad Estática , Sístole/efectos de los fármacos
19.
Nutrients ; 13(8)2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34445036

RESUMEN

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.


Asunto(s)
Anorexia Nerviosa/etiología , Anorexia Nerviosa/fisiopatología , Restricción Calórica , Sistema Cardiovascular/inervación , Carrera , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/fisiopatología , Adiposidad , Animales , Anorexia Nerviosa/diagnóstico por imagen , Anorexia Nerviosa/patología , Sistema Nervioso Autónomo/fisiopatología , Modelos Animales de Enfermedad , Femenino , Hemodinámica , Humanos , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Folículo Ovárico/patología , Ratas Wistar , Factores de Tiempo , Útero/patología , Pérdida de Peso
20.
Materials (Basel) ; 14(3)2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33573366

RESUMEN

Methods of spatiotemporal characterization of nonequilibrated polymer based matrices are still immature and imperfect. The purpose of the study was to develop the methodology for the spatiotemporal characterization of water transport and properties in alginate tablets under hydration. The regions of low water content were spatially and temporally sampled using Karl Fisher and Differential Scanning Callorimetry (spatial distribution of freezing/nonfreezing water) with spatial resolution of 1 mm. In the regions of high water content, where sampling was infeasible due to gel/sol consistency, magnetic resonance imaging (MRI) enabled characterization with an order of magnitude higher spatial resolution. The minimally hydrated layer (MHL), infiltration layer (IL) and fully hydrated layer (FHL) were identified in the unilaterally hydrated matrices. The MHL gained water from the first hour of incubation (5-10% w/w) and at 4 h total water content was 29-39% with nonfreezing pool of 28-29%. The water content in the IL was 45-47% and at 4 h it reached ~50% with the nonfreezing pool of 28% and T2 relaxation time < 10 ms. The FHL consisted of gel and sol layer with water content of 85-86% with a nonfreezing pool of 11% at 4 h and T2 in the range 20-200 ms. Hybrid destructive/nondestructive analysis of alginate matrices under hydration was proposed. It allowed assessing the temporal changes of water distribution, its mobility and interaction with matrices in identified layers.

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