scholarly journals Modelling drug transport during intraperitoneal chemotherapy

2017 ◽  
Vol 2 (2) ◽  
pp. 73-83 ◽  
Author(s):  
Margo Steuperaert ◽  
Charlotte Debbaut ◽  
Patrick Segers ◽  
Wim Ceelen
Keyword(s):  
Transport Process ◽  
Drug Transport ◽  
Lumped Parameter Model ◽  
Distributed Model ◽  
Tissue Properties ◽  
Multiple Parameters ◽  
Mass Transport Process ◽  
Actual Use ◽  
Transport Barriers

AbstractDespite a strong rationale for intraperitoneal (IP) chemotherapy, the actual use of the procedure is limited by the poor penetration depth of the drug into the tissue. Drug penetration into solid tumours is a complex mass transport process that involves multiple parameters not only related to the used cytotoxic agent but also to the tumour tissue properties and even the therapeutic setup. Mathematical modelling can provide unique insights into the different transport barriers that occur during IP chemotherapy as well as offer the possibility to test different protocols or drugs without the need for in vivo experiments. In this work, a distinction is made between three different types of model: the lumped parameter model, the distributed model and the cell-based model. For each model, we discuss which steps of the transport process are included and where assumptions are made. Finally, we focus on the advantages and main limitations of each category and discuss some future perspectives for the modelling of IP chemotherapy.

Bioprinted Nanoparticles for Tissue Engineering Applications

2009 ◽  
Author(s):  
Kivilcim Buyukhatipoglu ◽  
Robert Chang ◽  
Wei Sun ◽  
Alisa Morss Clyne
Keyword(s):  
Tissue Engineering ◽  
Tissue Growth ◽  
Bioactive Components ◽  
Engineering Applications ◽  
Tissue Properties ◽  
Native Tissue ◽  
3D Architecture

Tissue engineering may require precise patterning of cells and bioactive components to recreate the complex, 3D architecture of native tissue. However, it is difficult to image and track cells and bioactive factors once they are incorporated into the tissue engineered construct. These bioactive factors and cells may also need to be moved during tissue growth in vitro or after implantation in vivo to achieve the desired tissue properties, or they may need to be removed entirely prior to implantation for biosafety concerns.

scholarly journals The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5629
Author(s):  
Douglas B. Kell
Keyword(s):  
Lipid Bilayers ◽  
Drug Targets ◽  
Drug Transport ◽  
Phospholipid Bilayer ◽  
Substrate Uptake ◽  
Pharmaceutical Drugs ◽  
Natural Evolution ◽  
Lipid Ii ◽  
High Concentrations

Over the years, my colleagues and I have come to realise that the likelihood of pharmaceutical drugs being able to diffuse through whatever unhindered phospholipid bilayer may exist in intact biological membranes in vivo is vanishingly low. This is because (i) most real biomembranes are mostly protein, not lipid, (ii) unlike purely lipid bilayers that can form transient aqueous channels, the high concentrations of proteins serve to stop such activity, (iii) natural evolution long ago selected against transport methods that just let any undesirable products enter a cell, (iv) transporters have now been identified for all kinds of molecules (even water) that were once thought not to require them, (v) many experiments show a massive variation in the uptake of drugs between different cells, tissues, and organisms, that cannot be explained if lipid bilayer transport is significant or if efflux were the only differentiator, and (vi) many experiments that manipulate the expression level of individual transporters as an independent variable demonstrate their role in drug and nutrient uptake (including in cytotoxicity or adverse drug reactions). This makes such transporters valuable both as a means of targeting drugs (not least anti-infectives) to selected cells or tissues and also as drug targets. The same considerations apply to the exploitation of substrate uptake and product efflux transporters in biotechnology. We are also beginning to recognise that transporters are more promiscuous, and antiporter activity is much more widespread, than had been realised, and that such processes are adaptive (i.e., were selected by natural evolution). The purpose of the present review is to summarise the above, and to rehearse and update readers on recent developments. These developments lead us to retain and indeed to strengthen our contention that for transmembrane pharmaceutical drug transport “phospholipid bilayer transport is negligible”.

scholarly journals Hydrogel Tissue Construct-Based High-Content Compound Screening

2010 ◽  
Vol 16 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Vy Lam ◽  
Tetsuro Wakatsuki
Keyword(s):  
Kinase Inhibitor ◽  
Physiological Mechanism ◽  
Rho Kinase ◽  
Assay System ◽  
Physiological Status ◽  
Multiple Parameters ◽  
Compound Screening ◽  
Tissue Construct

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)–based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds—rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)—for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

In Vitro–In Vivo Scale-up of Drug Transport Activities

2007 ◽  
pp. 557-588 ◽  
Author(s):  
Kazuya Maeda ◽  
Yuichi Sugiyama
Keyword(s):  
Drug Transport ◽  
Scale Up

Polymer-dendrimer hybrids as carriers of anticancer agents

2021 ◽  
Vol 22 ◽  
Author(s):  
Guillermo Leobardo Rodríguez-Acosta ◽  
Carlos Hernández-Montalbán ◽  
María Fernanda Sabrina Vega-Razo ◽  
Irving Osiel Castillo-Rodríguez ◽  
Marcos Martínez-García
Keyword(s):  
Anticancer Agents ◽  
Drug Transport ◽  
Dendritic Structure ◽  
Polymeric Materials ◽  
Bioactive Molecules ◽  
Future Application ◽  
Linear Polymers ◽  
Host Interaction

: In recent years, polymeric materials with the ability to self-assemble into micelles have been increasingly investigated for application in various fields, mainly in biomedicine. Micellar morphology is important and interesting in the field of drug transport and delivery, since micelles can encapsulate hydrophobic molecules in their nucleus, improve the solubility of drugs, have active molecules in their outer layer, and, due to their nanometric size, they can take advantage of the EPR effect, prolong circulation time and avoid renal clearance. Furthermore, bioactive molecules (could be joined covalently or by host-host interaction) such as drugs, bioimaging molecules, proteins, targeting ligands, "cross-linkable" molecules, or linkages sensitive to internal or external stimuli can be incorporated into them. The confined multivalent cooperativity and the ability to modify the dendritic structure provide the versatility to create and improve the amphiphiles used in the micellar supramolecular field. As discussed in this review, the most studied structures are hybrid copolymers, which are formed by the combination of linear polymers and dendrons. Amphiphilic dendrimer micelles have achieved efficient and promising results in both in vitro and in vivo tests, and this encourages research for their future application in nanotherapies.

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.

Drug Delivery Devices and Targeting Agents for Platinum(II) Anticancer Complexes

2008 ◽  
Vol 61 (9) ◽  
pp. 675 ◽  
Author(s):  
Anwen M. Krause-Heuer ◽  
Maxine P. Grant ◽  
Nikita Orkey ◽  
Janice R. Aldrich-Wright
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Anticancer Agents ◽  
Drug Transport ◽  
Water Solubility ◽  
Controlled Drug Release ◽  
Drug Bioavailability ◽  
Platinum Drug ◽  
Drug Delivery Devices

An ideal platinum-based delivery device would be one that selectively targets cancerous cells, can be systemically delivered, and is non-toxic to normal cells. It would be beneficial to provide drug delivery devices for platinum-based anticancer agents that exhibit high drug transport capacity, good water solubility, stability during storage, reduced toxicity, and enhanced anticancer activity in vivo. However, the challenges for developing drug delivery devices include carrier stability in vivo, the method by which extracellular or intracellular drug release is achieved, overcoming the various mechanisms of cell resistance to drugs, controlled drug release to cancer cells, and platinum drug bioavailability. There are many potential candidates under investigation including cucurbit[n]urils, cyclodextrins, calix[n]arenes, and dendrimers, with the most promising being those that are synthetically adaptable enough to attach to targeting agents.

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