scholarly journals The Application of Targeted Nanodrugs with Dual Responsiveness of PH and Ros in Preventing and Treating Vascular Restenosis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jin Zhang
Keyword(s):  
Early Stage ◽  
Mass Ratio ◽  
Ph Responsive ◽  
Responsive Materials ◽  
Dual Responsive ◽  
Gene Vectors ◽  
Model Drug ◽  
Pass Through ◽  
Vascular Restenosis

In order to study the application of PH- and Ros-responsive targeted nanodrugs in preventing and treating vascular restenosis, a method based on pH-responsive and reactive oxygen species- (ROS-) responsive carrier materials synthesized in the early stage and rapamycin as a model drug was proposed. This method evaluated the therapeutic advantages of PH and Ros dual-responsive nanoparticles and the effect of dual-responsive active targeted drug delivery nanoparticles on vascular restenosis in vivo by comparing with nonresponsive PH or Ros single responsive nanotherapy. By optimizing the feed mass ratio of pH-responsive materials (ACD) and ROS-responsive materials (OCD), the best pH and ROS responsive nanoparticles were prepared. It has been proved that nanoparticles have ultrasmall volume (10–1000 nm) and can easily pass through the blood vessel wall without causing damage and have the characteristics of targeting and sustained release, so they are an ideal carrier for local administration. Nanoparticles as gene vectors have also achieved good results.

scholarly journals pH-Control in Aptamer-Based Diagnostics, Therapeutics, and Analytical Applications

2018 ◽  
Vol 11 (3) ◽  
pp. 80 ◽  
Author(s):  
Micaela Belleperche ◽  
Maria DeRosa
Keyword(s):  
Nucleic Acid ◽  
Targeted Delivery ◽  
Ph Control ◽  
Ph Responsive ◽  
Acid Base ◽  
Responsive Materials ◽  
Nucleic Acid Base ◽  
And Control ◽  
In Vivo Delivery

Aptamer binding has been used effectively for diagnostics, in-vivo targeting of therapeutics, and the construction and control of nanomachines. Nanostructures that respond to pH by releasing or changing affinity to a target have also been used for in vivo delivery, and in the construction of sensors and re-usable nanomachines. There are many applications that use aptamers together with pH-responsive materials, notably the targeted delivery of chemotherapeutics. However, the number of reported applications that directly use pH to control aptamer binding is small. In this review, we first discuss the use of aptamers with pH-responsive nanostructures for chemotherapeutic and other applications. We then discuss applications that use pH to denature or otherwise disrupt the binding of aptamers. Finally, we discuss motifs using non-canonical nucleic acid base pairing that can shift conformation in response to pH, followed by an overview of engineered pH-controlled aptamers designed using those motifs.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

Preparation and Evaluation of a Gas Formation-based Multiple-Unit Gastro-Retentive Floating Delivery System of Dipyridamole

2012 ◽  
Vol 5 (1) ◽  
pp. 1607-1616
Author(s):  
Y. Madhusudan Rao ◽  
Katakam V V ◽  
S Reddy ◽  
J M Somagoni ◽  
P K Panakanti ◽  
...  
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Polymeric Membrane ◽  
Wet Granulation ◽  
Physical Parameters ◽  
Gastric Residence Time ◽  
Gas Formation ◽  
Multiple Unit ◽  
Model Drug

The aim of this study was to prepare mini tablets to be filled into a capsule that is designed to float on the gastric contents based on gas formation technique. The drug-containing core mini-tablets were prepared by wet granulation method followed by a coating of the core units with seal coating, an effervescent layer and a gas-entrapping polymeric membrane (Eudragit RS30D, RL30D). Dipyridamole, which is predominantly absorbed in the upper part of GI tract and unabsorbed/insoluble at the lower intestine, was used as a model drug. The effect of the preparative parameters like amount of the effervescent agent layered onto the seal coated units, type and coating level of the gas-entrapping polymeric membrane, floating ability and drug release properties of the multiple-unit FDDS were evaluated. The formulations were evaluated for pharmacopoeial quality control tests. Physical parameters were found to be within the acceptable limits. The system using Eudragit® RL30D as a gas-entrapping polymeric membrane exhibited floating properties. The time to float decreased as amount of the effervescent agent increased and coating level of gas-entrapping polymeric membrane decreased. The optimum system exhibited complete floating within 3 minutes and maintained that buoyancy over a period of 8 hours. The drug release was sustained and linear with the square root of time. Increasing the coating level of the gas-entrapping polymeric membrane decreased drug release. Both the rapid-floating and sustained-release properties were achieved in the multiple-unit floating delivery system developed in this study. The in vivo gastric residence time was examined by radiograms and it was found that the units remained in the stomach for about 6 hours. The analysis of the dissolution data after storage at 40°C and 75% RH for 6 months showed no significant change indicating good stability.

scholarly journals Perivascular vital cells in the ablation center after multibipolar radiofrequency ablation in an in vivo porcine model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
F. G. M. Poch ◽  
C. A. Neizert ◽  
B. Geyer ◽  
O. Gemeinhardt ◽  
S. M. Niehues ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Early Stage ◽  
Pringle Maneuver ◽  
Vessel Diameter ◽  
Inflow Occlusion ◽  
White Zone ◽  
Cell Vitality ◽  
Internally Cooled ◽  
Hepatic Vessels

AbstractMultibipolar radiofrequency ablation (RFA) is an advanced ablation technique for early stage hepatocellular carcinoma and liver metastases. Vessel cooling in multibipolar RFA has not been systematically investigated. The objective of this study was to evaluate the presence of perivascular vital cells within the ablation zone after multibipolar RFA. Multibipolar RFA were performed in domestic pigs in vivo. Three internally cooled bipolar RFA applicators were used simultaneously. Three experimental settings were planned: (1) inter-applicator-distance: 15 mm; (2) inter-applicator-distance: 20 mm; (3) inter-applicator-distance: 20 mm with hepatic inflow occlusion (Pringle maneuver). A vitality staining was used to analyze liver cell vitality around all vessels in the ablation center with a diameter > 0.5 mm histologically. 771 vessels were identified. No vital tissue was seen around 423 out of 429 vessels (98.6%) situated within the central white zone. Vital cells could be observed around major hepatic vessels situated adjacent to the ablation center. Vessel diameter (> 3.0 mm; p < 0.05) and low vessel-to-ablation-center distance (< 0.2 mm; p < 0.05) were identified as risk factors for incomplete ablation adjacent to hepatic vessels. The vast majority of vessels, which were localized in the clinically relevant white zone, showed no vital perivascular cells, regardless of vessel diameter and vessel type. However, there was a risk of incomplete ablation around major hepatic vessels situated directly within the ablation center. A Pringle maneuver could avoid incomplete ablations.

scholarly journals Probing the Intracellular Bio-Nano Interface in Different Cell Lines with Gold Nanostars

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1183
Author(s):  
Cecilia Spedalieri ◽  
Gergo Péter Szekeres ◽  
Stephan Werner ◽  
Peter Guttmann ◽  
Janina Kneipp
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Early Stage ◽  
Protein Corona ◽  
Fibroblast Cell ◽  
Ultrastructural Level ◽  
Epithelial Cell Line ◽  
Animal Cells ◽  
Gold Nanostars

Gold nanostars are a versatile plasmonic nanomaterial with many applications in bioanalysis. Their interactions with animal cells of three different cell lines are studied here at the molecular and ultrastructural level at an early stage of endolysosomal processing. Using the gold nanostars themselves as substrate for surface-enhanced Raman scattering, their protein corona and the molecules in the endolysosomal environment were characterized. Localization, morphology, and size of the nanostar aggregates in the endolysosomal compartment of the cells were probed by cryo soft-X-ray nanotomography. The processing of the nanostars by macrophages of cell line J774 differed greatly from that in the fibroblast cell line 3T3 and in the epithelial cell line HCT-116, and the structure and composition of the biomolecular corona was found to resemble that of spherical gold nanoparticles in the same cells. Data obtained with gold nanostars of varied morphology indicate that the biomolecular interactions at the surface in vivo are influenced by the spike length, with increased interaction with hydrophobic groups of proteins and lipids for longer spike lengths, and independent of the cell line. The results will support optimized nanostar synthesis and delivery for sensing, imaging, and theranostics.

scholarly journals SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

2021 ◽  
Vol 11 (5) ◽  
pp. 431
Author(s):  
Sabine Hofer ◽  
Norbert Hofstätter ◽  
Albert Duschl ◽  
Martin Himly
Keyword(s):  
Risk Factor ◽  
Particle Deposition ◽  
Early Stage ◽  
Severe Disease ◽  
Ambient Air ◽  
Aerosol Deposition ◽  
Pulmonary Involvement ◽  
Mild Disease ◽  
Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

Yolk–shell magnetic composite Fe3O4@Co/Zn-ZIF for MR imaging-guided chemotherapy of tumors in vivo

2021 ◽  
Author(s):  
Ying Li ◽  
Lu-Lu Jiang ◽  
Ya-Xian Qiao ◽  
Dong Wan ◽  
Yan-Feng Huang
Keyword(s):  
Mr Imaging ◽  
Contrast Enhancement ◽  
Magnetic Composite ◽  
Loading Capacity ◽  
Ph Responsive

The yolk–shell composites Fe3O4@Co/Zn-ZIF exhibited high doxorubicin loading capacity, pH-responsive release characteristics, and strong T2-weighted MR imaging contrast enhancement, and were used for MR imaging-guided chemotherapy of tumors in vivo.

scholarly journals Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Lixia Ji ◽  
Lixia Cheng ◽  
Zhihong Yang
Keyword(s):  
Osmotic Stress ◽  
Early Stage ◽  
Lens Epithelial Cells ◽  
Anterior Capsule ◽  
Glycoprotein P ◽  
Protein Levels ◽  
P Glycoprotein ◽  
Sugar Cataract

Objective.Lens osmotic expansion, provoked by overactivated aldose reductase (AR), is the most essential event of sugar cataract. Chloride channel 3 (Clcn3) is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp) acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract.Methods and Results.In vitro, lens epithelial cells (LECs) were primarily cultured in gradient galactose medium (10–60 mM), more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day.Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

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