Intracellular Delivery Ii
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Intracellular Delivery Ii
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Author : Aleš Prokop
language : en
Publisher: Springer
Release Date : 2014-05-20
Intracellular Delivery Ii written by Aleš Prokop and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-05-20 with Medical categories.
This volume is a continuation of Volume 1 following the previously published Editorial. More emphasis is given to novel nanocarrier designs, their characterization and function, and applications for drug discovery and treatment. A number of chapters will deal with nanofibers as a new major application within the biomedical field with a very high success rate particularly in wound healing and diabetic foot and spine injuries. A major new subdivision will deal with mathematical methods for the assembly of nanocarriers both for simulation and function.
Targeted Intracellular Drug Delivery By Receptor Mediated Endocytosis
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Author : Padma V. Devarajan
language : en
Publisher: Springer Nature
Release Date : 2019-11-09
Targeted Intracellular Drug Delivery By Receptor Mediated Endocytosis written by Padma V. Devarajan and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-11-09 with Medical categories.
This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.
Intracellular Delivery Vehicles Based On 2 Methacryloyloxy Ethyl Phosphorylcholine
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Author : Nicholas John Warren
language : en
Publisher:
Release Date : 2012
Intracellular Delivery Vehicles Based On 2 Methacryloyloxy Ethyl Phosphorylcholine written by Nicholas John Warren and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Peptide Based Intracellular Delivery
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Author : Isaac Abrrey Monreal
language : en
Publisher:
Release Date : 2016
Peptide Based Intracellular Delivery written by Isaac Abrrey Monreal and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Drug delivery systems categories.
The ability to access intracellular targets is of vital importance, especially as the number of druggable intracellular targets being identified increases greatly every year. Intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes hindering their practical application in medicinal development. Our research seeks to approach this problem using two unique peptide based approaches capable of improving on current peptide based intracellular delivery technologies. Our first approach is to functionalize oligomeric versions of an existing HIV-TAT peptide transduction domain capable of orthogonal cargo attachment. The second approach is the de novo generation of a new class of unnatural peptides based on a neuraminic acid scaffold amenable to traditional Fmoc based solid phase peptide synthesis with expected tunable secondary structures and enhanced biostability. Both approaches afford adaptability to expected potential problems and pose an exciting addition to the toolset for use in delivering cargos to increasingly important intracellular targets.
Intracellular Delivery
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Author : Aleš Prokop
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-05-26
Intracellular Delivery written by Aleš Prokop and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-05-26 with Science categories.
This book features a special subsection of Nanomedicine, an application of nanotechnology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact significantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanodelivery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great interest. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.
Mechanisms Of Carrier Mediated Intracellular Delivery Of Therapeutics
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Author : Gilles Divita
language : en
Publisher:
Release Date : 2006
Mechanisms Of Carrier Mediated Intracellular Delivery Of Therapeutics written by Gilles Divita and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
Photothermal Intracellular Delivery Platforms
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Author : Tianxing Man
language : en
Publisher:
Release Date : 2020
Photothermal Intracellular Delivery Platforms written by Tianxing Man and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
Intracellular delivery of diverse biomolecules, such as protein, nucleic acids, nano-devices, has been of great importance and interest in biomedical fields like cancer therapy, gene editing and intracellular environment probing. Although tremendous effort has been expended, it remains challenging for existing transfer platforms to meet the emerging requirements of the cutting-edge research. In this thesis, I focused on three major hurdles in the current intracellular delivery, which are suspension cell delivery, complexity of incorporating nanotechnology, and large cargo delivery. Photothermal mechanism is the underlying physics throughout all the work to be introduced here. It utilizes the light energy and transforms it into thermal energy and then into mechanical energy, serving for different functions in delivery. Nanosecond laser was chosen as the original power tool due to its high energy density, remote operation capability, and selective absorption. The combination of laser and micro/nano structure has been extensively explored to develop various delivery capabilities. The first problem tackled in this thesis is to deliver materials into suspension cells with high efficiency, viability, and throughput. Suspension cells, especially lymphocytes, which represent 25-30% of immune cells, are of great interest in cancer immunotherapies and known as hard-to-transfect cells. To achieve effective delivery, the microwell structure with metallic sharp tips were designed to provide both cell anchoring and controllable membrane disruption on each cell. Suspension cells self- position by gravity within each microwell in direct contact with eight sharp tips, where laser-induced cavitation bubbles generate transient pores in the cell membrane to facilitate intracellular delivery of extracellular cargo. A range of cargo sizes were tested on this platform using Ramos suspension B cells with an efficiency of >84% for Calcein green (0.6 kDa) and >45% for FITC-dextran (2000 kDa), with retained viability of >96% and a throughput of >100 000 cells delivered per minute. The bacterial enzyme -lactamase (29 kDa) was delivered into Ramos B cells and retained its biological activity, whereas a green fluorescence protein expression plasmid was delivered into Ramos B cells with a transfection efficiency of >58%, and a viability of >89% achieved. The second problem raised from the notice of the huge potential of nanostructures, especially combined with photothermal mechanism, in contrast with their current limited applications in this field. Nanostructures, such as nanoneedle array, have been adopted in the intracellular delivery field due to its unique scale advantages, including minimal damage of the cell membrane and large cargo loading capacity from high surface-to-volume ratio. However, nanotechnologies have suffered from its complexity of high-precision fabrication and are limited to small area. Thus, we demonstrate the fabrication of large-area plasmonic gold (Au) nanodisk arrays that enable photothermal intracellular delivery of biomolecular cargo at high efficiency. The Au nanodisks (350 nm in diameter) were fabricated using chemical lift-off lithography (CLL), a high-throughput and low-cost for nanoscale chemical patterning. This technique is applied to produce Au nanostructures on a variety of substrates (e.g., silicon, glass, and plastic), which facilitate in situ intracellular delivery in laboratory cell culture environments, enabling integration with existing medical devices. Nanosecond laser pulses were used to excite the plasmonic nanostructures, thereby generating transient pores at the outer membranes of targeted cells that enable the delivery of biomolecules via diffusion. We studied nanodisks of various sizes and found that an increase in delivery efficiency correlated with decreasing disk radius, which we attribute to higher density of pores per cell. Delivery efficiencies of >98% were achieved with 1- m Au plasmonic disk arrays, using the cell impermeable dye Calcein (0.6 kDa) as a model payload, while maintaining cell viabilities at >98%. The highly efficient intracellular delivery approach demonstrated in this work will facilitate translational studies targeting molecular screening and drug testing that bridge laboratory and clinical investigations. Despite that major problems were nicely solved in the prior two projects, an apparent drawback appears, as the delivery efficiency drops significantly when cargo size increases. Photothermal energy was adopted, in both projects, to generate bubble explosion near the adjacent cell membrane so as to disrupt the membrane. Cargoes had to passively diffuse into the membrane, which posed the hardship to large cargoes. Thus, in the third project, the integration of membrane disruption and active pumping was studied to facilitate large cargo delivery with precise control and large-area uniformity. We utilized the high initial pressure of the laser-induced bubbles as the pump source for high-speed fluidic jet, which cuts the cell membrane and delivers cargos into the cytosol and nucleus. The fabrication processes of the devices are designed to be conventional and simple with large-area uniformity. The penetration was demonstrated by injecting 140 nm polystyrene beads into Agarose hydrogel which was prepared to have similar Young's Modulus as cells. With delicate device designs, we achieved penetration depths from tens of microns to a hundred microns, indicating the capability of three-dimensional tissue delivery and epidermal in vivo delivery, besides intracellular delivery into single layer of cells.
Intracellular Delivery Of Active Proteins And Genes Via Erodible Nanospheres
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Author : Maryellen Sandor
language : en
Publisher:
Release Date : 2002
Intracellular Delivery Of Active Proteins And Genes Via Erodible Nanospheres written by Maryellen Sandor and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Drug delivery systems categories.
Development Of Ph Responsive Nano Polyplexes For Intracellular Delivery Of Therapeutic Biomacromolecules
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Author : Brian Connor Evans
language : en
Publisher:
Release Date : 2015
Development Of Ph Responsive Nano Polyplexes For Intracellular Delivery Of Therapeutic Biomacromolecules written by Brian Connor Evans and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Electronic dissertations categories.
Intracellular Delivery Iii
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Author : Aleš Prokop
language : en
Publisher: Springer
Release Date : 2016-10-31
Intracellular Delivery Iii written by Aleš Prokop and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-10-31 with Medical categories.
A critical review is attempted to assess the status of nanomedicine entry onto the market. The emergence of new potential therapeutic entities such as DNA and RNA fragments requires that these new “drugs” will need to be delivered in a cell-and organelle-specific manner. Although efforts have been made over the last 50 years or so to develop such delivery technology, no effective and above all clinically approved protocol for cell-specific drug delivery in humans exists as yet. Various particles, macromolecules, liposomes and most recently “nanomaterials” have been said to “show promise” but none of these promises have so far been “reduced” to human clinical practice. The focus of this volume is on cancer indication since the majority of published research relates to this application; within that, we focus on solid tumors (solid malignancies). Our aim is critically to evaluate whether nanomaterials, both non-targeted and targeted to specific cells, could be of therapeutic benefit in clinical practice. The emphasis of this volume will be on pharmacokinetics (PK) and pharmacodynamics (PD) in animal and human studies. Apart from the case of exquisitely specific antibody-based drugs, the development of target-specific drug–carrier delivery systems has not yet been broadly successful at the clinical level. It can be argued that drugs generated using the conventional means of drug development (i.e., relying on facile biodistribution and activity after (preferably) oral administration) are not suitable for a target-specific delivery and would not benefit from such delivery even when a seemingly perfect delivery system is available. Therefore, successful development of site-selective drug delivery systems will need to include not only the development of suitable carriers, but also the development of drug entities that meet the required PK/PD profile.
