Effect of a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to Ex Vivo Lungs

2021 ◽  
Author(s):  
Nicholas D. Hages ◽  
John C. Sembrat ◽  
Lawrence Weber ◽  
Darragh J. Johnston ◽  
Amy Z. Stetten ◽  
...  
Keyword(s):  
Drug Transport ◽  
Ex Vivo ◽  
Aerosol Delivery ◽  
Distribution Uniformity ◽  
Surfactant Additive

scholarly journals Sequential deconstruction of composite drug transport in metastatic breast cancer

2020 ◽  
Vol 6 (26) ◽  
pp. eaba4498 ◽  
Author(s):  
Shreya Goel ◽  
Guodong Zhang ◽  
Prashant Dogra ◽  
Sara Nizzero ◽  
Vittorio Cristini ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Transport ◽  
Ex Vivo ◽  
Metastatic Breast ◽  
Lesion Size ◽  
Whole Body ◽  
High Temporal Resolution ◽  
Breast Cancers ◽  
Advanced Therapies

It is challenging to design effective drug delivery systems (DDS) that target metastatic breast cancers (MBC) because of lack of competent imaging and image analysis protocols that suitably capture the interactions between DDS and metastatic lesions. Here, we integrate high temporal resolution of in vivo whole-body PET-CT, ex vivo whole-organ optical imaging, high spatial resolution of confocal microscopy, and mathematical modeling, to systematically deconstruct the trafficking of injectable nanoparticle generators encapsulated with polymeric doxorubicin (iNPG-pDox) in pulmonary MBC. iNPG-pDox accumulated substantially in metastatic lungs, compared to healthy lungs. Intratumoral distribution and retention of iNPG-pDox varied with lesion size, possibly induced by locally remodeled microenvironment. We further used multiscale imaging and mathematical simulations to provide improved drug delivery strategies for MBC. Our work presents a multidisciplinary translational toolbox to evaluate transport and interactions of DDS within metastases. This knowledge can be recursively applied to rationally design advanced therapies for metastatic cancers.

scholarly journals Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1640
Author(s):  
Sreeja C. Nair ◽  
Kollencheri Puthenveettil Vinayan ◽  
Sabitha Mangalathillam
Keyword(s):  
Drug Release ◽  
Olfactory Epithelium ◽  
Drug Transport ◽  
Ex Vivo ◽  
Medical Attention ◽  
Pharmacokinetic Studies ◽  
Phenytoin Sodium ◽  
Drug Solution

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

scholarly journals Drug transport across the human placenta: review of placenta-on-a-chip and previous approaches

2019 ◽  
Vol 9 (5) ◽  
pp. 20190031 ◽  
Author(s):  
Rajeendra L. Pemathilaka ◽  
David E. Reynolds ◽  
Nicole N. Hashemi
Keyword(s):  
Drug Transport ◽  
Ex Vivo ◽  
Drug Intake ◽  
Pharmaceutical Drugs ◽  
Pharmaceutical Drug ◽  
Scientific Disciplines ◽  
Study Of Medicine ◽  
Controversial Topic

In the past few decades, the placenta became a very controversial topic that has had many researchers and pharmacists discussing the significance of the effects of pharmaceutical drug intake and how it is a possible leading cause towards birth defects. The creation of an in vitro microengineered model of the placenta can be used to replicate the interactions between the mother and fetus, specifically pharmaceutical drug intake reactions. As the field of nanotechnology significantly continues growing, nanotechnology will become more apparent in the study of medicine and other scientific disciplines, specifically microengineering applications. This review is based on past and current research that compares the feasibility and testing of the placenta-on-a-chip microengineered model to the previous and underdeveloped in vivo and ex vivo approaches. The testing of the practicality and effectiveness of the in vitro , in vivo and ex vivo models requires the experimentation of prominent pharmaceutical drugs that most mothers consume during pregnancy. In this case, these drugs need to be studied and tested more often. However, there are challenges associated with the in vitro , in vivo and ex vivo processes when developing a practical placental model, which are discussed in further detail.

Intestinal drug transport: ex vivo evaluation of the interactions between ABC transporters and anthelmintic molecules

2014 ◽  
Vol 37 (4) ◽  
pp. 332-337 ◽  
Author(s):  
M. Ballent ◽  
L. Maté ◽  
G. Virkel ◽  
J. Sallovitz ◽  
P. Viviani ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Drug Transport ◽  
Ex Vivo ◽  
Intestinal Drug Transport

Aerosol delivery during spontaneous breathing with different types of nebulizers- in vitro/ex vivo models evaluation

2018 ◽  
Vol 48 ◽  
pp. 225-231 ◽  
Author(s):  
Hui-Ling Lin ◽  
Tien-Pei Fang ◽  
Hui-Sun Cho ◽  
Gwo-Hwa Wan ◽  
Meng-Jer Hsieh ◽  
...  
Keyword(s):  
Spontaneous Breathing ◽  
Ex Vivo ◽  
Aerosol Delivery ◽  
Different Types

Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

1989 ◽  
Vol 47 ◽  
pp. 886-887
Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Retention Data ◽  
Vascular Prostheses ◽  
Group 4 ◽  
Human Fibronectin ◽  
Insufficient Time ◽  
Group 3 ◽  
Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

The Shikani HME: A New Tracheostomy Heat and Moisture Exchanger

2020 ◽  
Vol 63 (9) ◽  
pp. 2921-2929
Author(s):  
Alan H. Shikani ◽  
Elamin M. Elamin ◽  
Andrew C. Miller
Keyword(s):  
Ex Vivo ◽  
Moisture Loss ◽  
Speaking Valve ◽  
Time Zero ◽  
In Series ◽  
Turbulent Airflow ◽  
The Difference ◽  
Loss Efficiency ◽  
Heat And Moisture ◽  
Lung Simulation

Purpose Tracheostomy patients face many adversities including loss of phonation and essential airway functions including air filtering, warming, and humidification. Heat and moisture exchangers (HMEs) facilitate humidification and filtering of inspired air. The Shikani HME (S-HME) is a novel turbulent airflow HME that may be used in-line with the Shikani Speaking Valve (SSV), allowing for uniquely preserved phonation during humidification. The aims of this study were to (a) compare the airflow resistance ( R airflow ) and humidification efficiency of the S-HME and the Mallinckrodt Tracheolife II tracheostomy HME (M-HME) when dry (time zero) and wet (after 24 hr) and (b) determine if in-line application of the S-HME with a tracheostomy speaking valve significantly increases R airflow over a tracheostomy speaking valve alone (whether SSV or Passy Muir Valve [PMV]). Method A prospective observational ex vivo study was conducted using a pneumotachometer lung simulation unit to measure airflow ( Q ) amplitude and R airflow , as indicated by a pressure drop ( P Drop ) across the device (S-HME, M-HME, SSV + S-HME, and PMV). Additionally, P Drop was studied for the S-HME and M-HME when dry at time zero (T 0 ) and after 24 hr of moisture testing (T 24 ) at Q of 0.5, 1, and 1.5 L/s. Results R airflow was significantly less for the S-HME than M-HME (T 0 and T 24 ). R airflow of the SSV + S-HME in series did not significant increase R airflow over the SSV or PMV alone. Moisture loss efficiency trended toward greater efficiency for the S-HME; however, the difference was not statistically significant. Conclusions The turbulent flow S-HME provides heat and moisture exchange with similar or greater efficacy than the widely used laminar airflow M-HME, but with significantly lower resistance. The S-HME also allows the innovative advantage of in-line use with the SSV, hence allowing concurrent humidification and phonation during application, without having to manipulate either device.

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