scholarly journals Pressure-Enabled Drug Delivery Approach in the Pancreas with Retrograde Venous Infusion of Lipiodol with Ex Vivo Analysis

2020 ◽  
Vol 44 (1) ◽  
pp. 141-149
Author(s):  
Aravind Arepally ◽  
James Chomas ◽  
Steven C. Katz ◽  
David Jaroch ◽  
K. Pallav Kolli ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
Signal To Noise Ratio ◽  
Three Dimensional ◽  
Organ Damage ◽  
Pancreatic Tissue ◽  
Histological Evaluation ◽  
Ethiodized Oil ◽  
Venous Infusion ◽  
Infusion System

Abstract Purpose To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach. Methods Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands. Results A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5–2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia. Conclusions PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study.

scholarly journals Simultaneous imaging of hard and soft biological tissues in a low-field dental MRI scanner

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José M. Algarín ◽  
Elena Díaz-Caballero ◽  
José Borreguero ◽  
Fernando Galve ◽  
Daniel Grau-Ruiz ◽  
...  
Keyword(s):  
Spatial Information ◽  
Ex Vivo ◽  
Signal To Noise Ratio ◽  
Spin Echo ◽  
Pulse Sequences ◽  
Three Dimensional ◽  
Biological Tissues ◽  
Human Teeth ◽  
Low Field ◽  
The Impact

AbstractMagnetic Resonance Imaging (MRI) of hard biological tissues is challenging due to the fleeting lifetime and low strength of their response to resonant stimuli, especially at low magnetic fields. Consequently, the impact of MRI on some medical applications, such as dentistry, continues to be limited. Here, we present three-dimensional reconstructions of ex-vivo human teeth, as well as a rabbit head and part of a cow femur, all obtained at a field strength of 260 mT. These images are the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and they have been acquired in a home-made, special-purpose, pre-medical MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We encode spatial information with two pulse sequences: Pointwise-Encoding Time reduction with Radial Acquisition and a new sequence we have called Double Radial Non-Stop Spin Echo, which we find to perform better than the former. For image reconstruction we employ Algebraic Reconstruction Techniques (ART) as well as standard Fourier methods. An analysis of the resulting images shows that ART reconstructions exhibit a higher signal-to-noise ratio with a more homogeneous noise distribution.

Cryomicroscopy of crotoxin complex crystals at 400 KV

1989 ◽  
Vol 47 ◽  
pp. 826-827
Author(s):  
Jaap Brink ◽  
Wah Chiu
Keyword(s):  
Signal To Noise Ratio ◽  
3D Structure ◽  
Three Dimensional ◽  
Carbon Films ◽  
Depth Of Field ◽  
Basic Subunit ◽  
Ewald Sphere ◽  
Diffraction Patterns ◽  
Complex Crystals ◽  
Acidic Subunit

The crotoxin complex is a potent neurotoxin composed of a basic subunit (Mr = 12,000) and an acidic subunit (M = 10,000). The basic subunit possesses phospholipase activity whereas the acidic subunit shows no enzymatic activity at all. The complex's toxocity is expressed both pre- and post-synaptically. The crotoxin complex forms thin crystals suitable for electron crystallography. The crystals diffract up to 0.16 nm in the microscope, whereas images show reflections out to 0.39 nm2. Ultimate goal in this study is to obtain a three-dimensional (3D-) structure map of the protein around 0.3 nm resolution. Use of 100 keV electrons in this is limited; the unit cell's height c of 25.6 nm causes problems associated with multiple scattering, radiation damage, limited depth of field and a more pronounced Ewald sphere curvature. In general, they lead to projections of the unit cell, which at the desired resolution, cannot be interpreted following the weak-phase approximation. Circumventing this problem is possible through the use of 400 keV electrons. Although the overall contrast is lowered due to a smaller scattering cross-section, the signal-to-noise ratio of especially higher order reflections will improve due to a smaller contribution of inelastic scattering. We report here our preliminary results demonstrating the feasability of the data collection procedure at 400 kV.Crystals of crotoxin complex were prepared on carbon-covered holey-carbon films, quench frozen in liquid ethane, inserted into a Gatan 626 holder, transferred into a JEOL 4000EX electron microscope equipped with a pair of anticontaminators operating at −184°C and examined under low-dose conditions. Selected area electron diffraction patterns (EDP's) and images of the crystals were recorded at 400 kV and −167°C with dose levels of 5 and 9.5 electrons/Å, respectively.

An Update on Recent Advances in Cubosome: A Novel Drug Delivery System

2021 ◽  
Vol 21 ◽  
Author(s):  
Madhukar Garg ◽  
Anju Goyal ◽  
Sapna Kumari
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Lipid Bilayers ◽  
Delivery System ◽  
Liquid Crystalline ◽  
Three Dimensional ◽  
Biologically Active ◽  
Potential Applications ◽  
Health Related ◽  
Novel Drug

: Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three dimensional honeycombs like structure provided with two internal aqueous channels for incorporation of number of biologically active ingredients. In contrast liposomes they provide large surface area for incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as method of choice in the sustained release, controlled release and targeted release dosage forms as new drug delivery system for the better release of the drugs. As lot of advancement in the new form of dosage form has bring the novel avenues in drug delivery mechanisms so it was matter of worth to compile the latest updates on the various aspects of mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health related benefits.

Functionally Tailored Electro-Sensitive Poly(Acrylamide)-g-Pectin Copolymer Hydrogel for Transdermal Drug Delivery Application: Synthesis, Characterization, In-vitro and Ex-vivo Evaluation

2020 ◽  
Vol 10 (3) ◽  
pp. 185-196
Author(s):  
Sudha B. Patil ◽  
Syed Z. Inamdar ◽  
Kakarla R. Reddy ◽  
Anjanapura V. Raghu ◽  
Krishnamachari G. Akamanchi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Transdermal Drug Delivery ◽  
Ex Vivo ◽  
Transmission Rate ◽  
Electric Signal ◽  
Poly Vinyl Alcohol ◽  
Electric Stimulus ◽  
Copolymer Hydrogel ◽  
Transdermal Drug Delivery Systems

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

scholarly journals Electrochemical treatment of ex vivo human abdominal skin and potential use in scar management: A pilot study

2021 ◽  
Vol 7 ◽  
pp. 205951312098853
Author(s):  
Dana M Hutchison ◽  
Amir A Hakimi ◽  
Avin Wijayaweera ◽  
Soohong Seo ◽  
Ellen M Hong ◽  
...  
Keyword(s):  
Color Change ◽  
Ex Vivo ◽  
Low Cost ◽  
Histological Evaluation ◽  
Ph Change ◽  
Level Of Evidence ◽  
Abdominal Skin ◽  
Electrochemical Therapy ◽  
Mean Width ◽  
Scar Management

Introduction: Scar treatments aim to address pathologic collagen deposition; however, they can be expensive or difficult to control. Electrochemical therapy (ECT) offers a simple alternative treatment. The purpose of this study is to examine the acid-base and histological changes in ex vivo human abdominal skin following ECT. Methods: Forty-two ex vivo human panniculus tissue sections collected from six individuals were tumesced with normal saline. ECT was performed by inserting two platinum needle electrodes connected to a DC power supply into each specimen. Voltage was varied (3–6 V) and applied for 5 minutes. Each specimen was sectioned across both electrode insertion sites and immediately stained with pH sensitive dye. The width of dye color change for each dosimetry pair was calculated. Hematoxylin and eosin staining was used to evaluate samples. Results and Discussion: ECT caused a spatially localised and dose-dependent increased area of acidic and basic pH around the anode and cathode, respectively. A significantly greater mean width of pH change was generated at the cathode compared to the anode in all treatment groups. Histological evaluation displayed broad condensation and hyalinisation of dermal collagen. Conclusion: ECT triggered dermal pH alterations and changed the underlying structural framework of the specimen. This technology may serve as a low-cost, minimally invasive local soft-tissue remodeling technique with potential application in scar management. Level of Evidence: 5 Lay Summary Electrochemical therapy is a novel treatment that causes spatially selective dermal injury in areas of interest. This study measures the effects of electrochemical therapy when applied to abdominal skin. Electrochemical therapy appears to have beneficial effects by causing a highly localised reduction in collagen content or local softening of tissue, which is consistent with other studies on scar therapies, including chemexfoliation, radiofrequency technologies, and lasers. However, electrochemical therapy can be performed at a fraction of the costs of these aforementioned modalities.

scholarly journals Application of Dendrimers for Treating Parasitic Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 343
Author(s):  
Veronica Folliero ◽  
Carla Zannella ◽  
Annalisa Chianese ◽  
Debora Stelitano ◽  
Annalisa Ambrosino ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Water Solubility ◽  
Parasitic Infection ◽  
Three Dimensional ◽  
Medical Knowledge ◽  
High Ratio ◽  
Molecular Volume ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Wide Range

Despite advances in medical knowledge, parasitic diseases remain a significant global health burden and their pharmacological treatment is often hampered by drug toxicity. Therefore, drug delivery systems may provide useful advantages when used in combination with conventional therapeutic compounds. Dendrimers are three-dimensional polymeric structures, characterized by a central core, branches and terminal functional groups. These nanostructures are known for their defined structure, great water solubility, biocompatibility and high encapsulation ability against a wide range of molecules. Furthermore, the high ratio between terminal groups and molecular volume render them a hopeful vector for drug delivery. These nanostructures offer several advantages compared to conventional drugs for the treatment of parasitic infection. Dendrimers deliver drugs to target sites with reduced dosage, solving side effects that occur with accepted marketed drugs. In recent years, extensive progress has been made towards the use of dendrimers for therapeutic, prophylactic and diagnostic purposes for the management of parasitic infections. The present review highlights the potential of several dendrimers in the management of parasitic diseases.

scholarly journals Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 544
Author(s):  
Miao Wang ◽  
Sung-Kyun You ◽  
Hong-Ki Lee ◽  
Min-Gu Han ◽  
Hyeon-Min Lee ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anticancer Agents ◽  
Lipid Membrane ◽  
Ex Vivo ◽  
System Optimization ◽  
Raw Material ◽  
Phospholipid Complex ◽  
Low Solubility

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.

scholarly journals Ab initiostructure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector

2016 ◽  
Vol 72 (2) ◽  
pp. 236-242 ◽  
Author(s):  
E. van Genderen ◽  
M. T. B. Clabbers ◽  
P. P. Das ◽  
A. Stewart ◽  
I. Nederlof ◽  
...  
Keyword(s):  
Electron Diffraction ◽  
Room Temperature ◽  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Three Dimensional ◽  
Direct Methods ◽  
Liquid Nitrogen Temperature ◽  
High Dynamic Range ◽  
Electron Diffraction Data ◽  
High Signal

Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enablingab initiophasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼0.013 e− Å−2 s−1) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS,SHELX) and for electron crystallography (ADT3D/PETS,SIR2014).

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