Contrasting Properties of Polymeric Nanocarriers for MRI-Guided Drug Delivery.

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.

Calcification alters the viscoelastic properties of tendon fascicle bundles depending on matrix content.

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.

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

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.

Ratiometric pH-Responsive 19F Magnetic Resonance Imaging Contrast Agents Based on Hydrazone Switches.

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.

Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application.

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).

In Vitro Wound Dressing Stack Model as a First Step to Evaluate the Behavior of Dressing Materials in Wound Bed-An Assessment of Mass Transport Phenomena in Hydrogel Wound Dressings.

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.

Hydration Patterns in Sodium Alginate Polymeric Matrix Tablets-The Result of Drug Substance Incorporation.

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.

The dispersion of viscoelastic properties of fascicle bundles within the tendon results from the presence of interfascicular matrix and flow of body fluids.

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.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

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.

Poly(Vinyl Alcohol) Cryogel Membranes Loaded with Resveratrol as Potential Active Wound Dressings.

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.

Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats.

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.

Spatiotemporal Analysis of Hydration Mechanism in Sodium Alginate Matrix Tablets.

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.

Effective Detection of Nafion®-Based Theranostic Nanocapsules through 19F Ultra-Short Echo Time MRI.

The application of the Three-Dimensional Ultra-Short Echo Time (3D UTE) pulse sequence at a high magnetic field for visualization of the distribution of 19F loaded theranostic core-shell nanocapsules with Nafion® (1,1,2,2-tetrafluoroethene; 1,1,2,2-tetrafluoro-2- [1,1,1,2,3,3-hexafluoro-3-(1,2,2-trifluoroethenoxy)propan-2-yl] oxyethanesulfonic acid) incorporated into the shell is presented. The nanocarriers were formed via the layer-by-layer technique with biodegradable polyelectrolytes: PLL (Poly-L-lysine), and with Nafion®: polymer with high 19F content. Before imaging, an MR (magnetic resonance) spectroscopy and T1 and T2 measurements were performed, resulting in values of T2 between 1.3 ms and 3.0 ms, depending on the spectral line. To overcome limitations due to such short T2, the 3D UTE pulse sequence was applied for 19F MR imaging. First Nafion® solutions of various concentrations were measured to check the detection limit of our system for the investigated molecule. Next, the imaging of a phantom containing core-shell nanocapsules was performed to assess the possibility of visualizing their distribution in the samples. Images of Nafion® containing samples with SNR ≥ 5 with acquisition time below 30 minutes for 19F concentration as low as 1.53·10-2 mmol 19F/g of sample, were obtained. This is comparable with the results obtained for molecules, which exhibit more preferable MR characteristics.

Nafion-Based Nanocarriers for Fluorine Magnetic Resonance Imaging.

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.

Hypothalamic and brain stem neurochemical profile in anorectic rats after peripheral administration of kisspeptin-10 using 1 H-nmr spectroscopy in vivo.

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.

Magnetically responsive polycaprolactone nanocarriers for application in the biomedical field: magnetic hyperthermia, magnetic resonance imaging, and magnetic drug delivery.

There are huge demands on multifunctional nanocarriers to be used in nanomedicine. Herein, we present a simple and efficient method for the preparation of multifunctional magnetically responsive polymeric-based nanocarriers optimized for biomedical applications. The hybrid delivery system is composed of drug-loaded polymer nanoparticles (poly(caprolactone), PCL) coated with a multilayer shell of polyglutamic acid (PGA) and superparamagnetic iron oxide nanoparticles (SPIONs), which are known as bio-acceptable components. The PCL nanocarriers with a model anticancer drug (Paclitaxel, PTX) were formed by the spontaneous emulsification solvent evaporation (SESE) method, while the magnetically responsive multilayer shell was formed via the layer-by-layer (LbL) method. As a result, we obtained magnetically responsive polycaprolactone nanocarriers (MN-PCL NCs) with an average size of about 120 nm. Using the 9.4 T preclinical magnetic resonance imaging (MRI) scanner we confirmed, that obtained MN-PCL NCs can be successfully used as a MRI-detectable drug delivery system. The magnetic hyperthermia effect of the MN-PCL NCs was demonstrated by applying a 25 mT radio-frequency (f = 429 kHz) alternating magnetic field. We found a Specific Absorption Rate (SAR) of 55 W g-1. The conducted research fulfills the first step of investigation for biomedical application, which is mandatory for the planning of any in vitro and in vivo studies.

Fe3O4@SiO2@Au nanoparticles for MRI-guided chemo/NIR photothermal therapy of cancer cells.

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe3O4@SiO2@Au nanoparticles (NPs) were designed. The encapsulation of Fe3O4 cores inside continuous SiO2 shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T 2 contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe3O4@SiO2@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm-2). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10-15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43-50%. This increase of the cytotoxic properties of the Fe3O4@SiO2@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.

An Inhalable Theranostic System for Local Tuberculosis Treatment Containing an Isoniazid Loaded Metal Organic Framework Fe-MIL-101-NH2-From Raw MOF to Drug Delivery System.

The theranostic approach to local tuberculosis treatment allows drug delivery and imaging of the lungs for a better control and personalization of antibiotic therapy. Metal-organic framework (MOF) Fe-MIL-101-NH2 nanoparticles were loaded with isoniazid. To optimize their functionality a 23 factorial design of spray-drying with poly(lactide-co-glycolide) and leucine was employed. Powder aerodynamic properties were assessed using a twin stage impinger based on the dose emitted and the fine particle fraction. Magnetic resonance imaging (MRI) contrast capabilities were tested on porous lung tissue phantom and ex vivo rat lungs. Cell viability and uptake studies were conducted on murine macrophages RAW 246.9. The final product showed good aerodynamic properties, modified drug release, easier uptake by macrophages in relation to raw isoniazid-MOF, and MRI contrast capabilities. Starting from raw MOF, a fully functional inhalable theranostic system with a potential application in personalized tuberculosis pulmonary therapy was developed.

Gadolinium labeled polyelectrolyte nanocarriers for theranostic application.

Here, we designed a novel Gadolinium (Gd) labeled drug-loaded polyelectrolyte nanocarriers for theranostics. The nanocarriers were formed via layer-by-layer technique with biodegradable polyelectrolytes: PLL (Poly-L-lysine), PLL-Gd (Gadolinium-labeled Poly-L-lysine) and PGA (Poly-L-glutamic acid). Anticancer drug (Paclitaxel) was encapsulated in the formed nanocarriers. The average size of synthesized nanocarriers was around 150 nm. The empty gadolinium labeled nanocarriers did not show any deleterious effects on tested cells (CT26-CEA, B16F10, 4T1 and PBMC), whereas encapsulated paclitaxel retained its cytotoxic/cytostatic activity. Using T2 and T1 NMR relaxation measurements with 9.4 T preclinical MRI scanner, we demonstrated that gadolinium labeled nanocarriers can be detected due to a locally altered contrast in the MR image. Thus, they may become a promising platform for future theranostic applications.

Use of ebselen as a neuroprotective agent in rat spinal cord subjected to traumatic injury.

Spinal cord injury (SCI) causes disturbances of motor skills. Free radicals have been shown to be essential for the development of spinal cord trauma. Despite some progress, until now no effective pharmacological therapies against SCI have been verified. The purpose of our experiment was to investigate the neuroprotective effects of ebselen on experimental SCI. Twenty-two rats subjected to SCI were randomly subjected to SCI with no further treatment (n = 10) or intragastric administration of ebselen (10 mg/kg) immediately and 24 hours after SCI. Behavioral changes were assessed using the Basso, Beattie, and Bresnahan locomotor scale and footprint test during 12 weeks after SCI. Histopathological and immunohistochemical analyses of spinal cords and brains were performed at 12 weeks after SCI. Magnetic resonance imaging analysis of spinal cords was also performed at 12 weeks after SCI. Rats treated with ebselen presented only limited neurobehavioral progress as well as reduced spinal cord injuries compared with the control group, namely length of lesions (cysts/scars) visualized histopathologically in the spinal cord sections was less but cavity area was very similar. The same pattern was found in T2-weighted magnetic resonance images (cavities) and diffusion-weighted images (scars). The number of FluoroGold retrogradely labeled neurons in brain stem and motor cortex was several-fold higher in ebselen-treated rats than in the control group. The findings suggest that ebselen has only limited neuroprotective effects on injured spinal cord. All exprimental procedures were approved by the Local Animal Ethics Committee for Experiments on Animals in Katowice (Katowice, Poland) (approval No. 19/2009).