Intracellular Delivery III

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Publisher : Springer
ISBN 13 : 3319435256
Total Pages : 455 pages
Book Rating : 4.3/5 (194 download)

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Book Synopsis Intracellular Delivery III by : Aleš Prokop

Download or read book Intracellular Delivery III written by Aleš Prokop and published by Springer. This book was released on 2016-10-31 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Intracellular Delivery

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Publisher : Springer Science & Business Media
ISBN 13 : 9400712480
Total Pages : 871 pages
Book Rating : 4.4/5 (7 download)

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Book Synopsis Intracellular Delivery by : Aleš Prokop

Download or read book Intracellular Delivery written by Aleš Prokop and published by Springer Science & Business Media. This book was released on 2011-05-26 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Intracellular Delivery II

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Publisher : Springer
ISBN 13 : 9401788960
Total Pages : 479 pages
Book Rating : 4.4/5 (17 download)

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Book Synopsis Intracellular Delivery II by : Aleš Prokop

Download or read book Intracellular Delivery II written by Aleš Prokop and published by Springer. This book was released on 2014-05-20 with total page 479 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 :
Publisher : Springer Nature
ISBN 13 : 3030291685
Total Pages : 560 pages
Book Rating : 4.0/5 (32 download)

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Book Synopsis Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis by : Padma V. Devarajan

Download or read book Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis written by Padma V. Devarajan and published by Springer Nature. This book was released on 2019-11-09 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

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Author :
Publisher : Springer
ISBN 13 : 9789400712492
Total Pages : 867 pages
Book Rating : 4.7/5 (124 download)

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Book Synopsis Intracellular Delivery by : Ales Prokop

Download or read book Intracellular Delivery written by Ales Prokop and published by Springer. This book was released on 2011-08-27 with total page 867 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Multifunctional Nanocarriers for Contemporary Healthcare Applications

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Author :
Publisher : IGI Global
ISBN 13 : 1522547827
Total Pages : 624 pages
Book Rating : 4.5/5 (225 download)

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Book Synopsis Multifunctional Nanocarriers for Contemporary Healthcare Applications by : Barkat, Md. Abul

Download or read book Multifunctional Nanocarriers for Contemporary Healthcare Applications written by Barkat, Md. Abul and published by IGI Global. This book was released on 2018-01-12 with total page 624 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in technology permeates every aspect of life, including the healthcare system. Nanotechnology based systems have gained popularity based upon their promise, size, and other characteristics. Multifunctional Nanocarriers for Contemporary Healthcare Applications is a critical academic publication that explores advancements in nanostructured systems, applications of these systems in healthcare, and biomedical applications of these systems. Featuring coverage on a wide range of topics, such as hydrogels, controlled drug delivery systems, and nanomedicine, this book is geared toward researchers, students, and academicians seeking current research on advancements and applications of nanostructured systems in the healthcare industry.

Intracellular Protein Delivery by Genetically Encoded and Structurally Constrained Cell-penetrating Peptides

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Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (115 download)

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Book Synopsis Intracellular Protein Delivery by Genetically Encoded and Structurally Constrained Cell-penetrating Peptides by : Kuangyu Chen (Ph. D. in chemistry)

Download or read book Intracellular Protein Delivery by Genetically Encoded and Structurally Constrained Cell-penetrating Peptides written by Kuangyu Chen (Ph. D. in chemistry) and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are valuable research tools and therapeutic agents, but their intracellular applications are limited by poor cell-permeability. Cell penetrating peptides (CPPs) are widely used carrier molecules for intracellular protein delivery. While CPPs can be assembled with protein cargos via different methods including genetic fusion, chemical ligation and physical complexation, each method has its own limitations. Inspired by our previous findings that structurally constrained small synthetic CPPs are highly efficient delivery carriers, we here developed a new protein delivery approach through which structurally constrained CPPs were genetically encoded into a protein of interest, thus to achieve high delivery efficiency, CPP stability and ease for production at the same time. The primary goal of my dissertation research is to engineer proteins of interest with intrinsic cell-permeability, by applying the technique that structurally constrained CPPs were incorporated into protein loop regions, resulting in functional delivery of different protein cargos inside the cells. We first identified several active CPP sequences by designing and characterizing a small group of cyclic peptide library. The insertion of selected CPPs into a solvent exposed loop of enhanced green fluorescence protein (EGFP) resulted in efficient intracellular delivery. We then applied this strategy to intracellular delivery of purine nucleoside phosphorylase (PNP), a protein missing in immunodeficiency diseases. Efficient delivery of PNP by loop-inserted CPP restored cytosolic enzyme activity in PNP deficient cells and corrected their metabolic defect, indicating significant therapeutic values of this approach. Next, to further enhance protein delivery efficiency, we incorporated non-proteinogenic building blocks into the loop-inserted CPPs via cysteine derivatization. Through screening a small library of different hydrophobic moieties, the cell-penetrating activity of engineered EGFP was increased by up to 15-fold. Finally, we successfully delivered an antibody fragment (nanobody) into the cells by inserting CPP sequence into one of its CDR loops. The engineered GFP binding nanobody (GBN) retained high antigen binding affinity and was able to selectively engage its antigen after cytosolic entry. These findings established a general approach to produce cell-permeable antibody fragments for intracellular targets.

Intracellular Delivery of Peptide Carriers, Substrates and Inhibitors

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Author :
Publisher : LAP Lambert Academic Publishing
ISBN 13 : 9783838344188
Total Pages : 304 pages
Book Rating : 4.3/5 (441 download)

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Book Synopsis Intracellular Delivery of Peptide Carriers, Substrates and Inhibitors by : Diarmaid Murphy

Download or read book Intracellular Delivery of Peptide Carriers, Substrates and Inhibitors written by Diarmaid Murphy and published by LAP Lambert Academic Publishing. This book was released on 2010-03 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: The lipid bilayer, which comprises all cell membranes, represents a formidable barrier to the delivery of large hydrophilic molecules into cells. The ability to introduce information-rich molecules into cells is a challenge in the development of new therapeutics for diseases not currently amenable to small molecule intervention. This work focuses on the delivery of peptide-based molecules including; inhibitors, substrates and carriers into cells. A series of peptide-based inhibitors against caspase-3, an intracellular enzyme involved in apoptosis, were assessed for their cell membrane permeability. Proteolytic activation of a cell penetrating peptide was also investigated as a means of controlling the uptake of these carrier peptides into cells. Finally, the uptake and processing of an internally quenched Tat-caspase substrate was examined in cells undergoing apoptosis. This book may be of interest to scientists working in any area where large molecules need to be effectively delivered to cells. It may be of particular interest to those working on cell penetrating peptides, proteases or apoptosis.

Photothermal Intracellular Delivery Platforms

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Publisher :
ISBN 13 :
Total Pages : 102 pages
Book Rating : 4.:/5 (116 download)

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Book Synopsis Photothermal Intracellular Delivery Platforms by : Tianxing Man

Download or read book Photothermal Intracellular Delivery Platforms written by Tianxing Man and published by . This book was released on 2020 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Therapeutic Intracellular Delivery Using Magnetic Fields, Nanoparticle Technology and Enhanced Cell Penetrating Peptides

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Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (133 download)

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Book Synopsis Therapeutic Intracellular Delivery Using Magnetic Fields, Nanoparticle Technology and Enhanced Cell Penetrating Peptides by : Lia Andrea Blokpoel Ferreras

Download or read book Therapeutic Intracellular Delivery Using Magnetic Fields, Nanoparticle Technology and Enhanced Cell Penetrating Peptides written by Lia Andrea Blokpoel Ferreras and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Trafficking Inside Cells

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Publisher : Springer Science & Business Media
ISBN 13 : 038793877X
Total Pages : 459 pages
Book Rating : 4.3/5 (879 download)

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Book Synopsis Trafficking Inside Cells by : Nava Segev

Download or read book Trafficking Inside Cells written by Nava Segev and published by Springer Science & Business Media. This book was released on 2010-05-30 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.

Molecular Biology of the Cell

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Publisher :
ISBN 13 : 9780815332183
Total Pages : 0 pages
Book Rating : 4.3/5 (321 download)

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Book Synopsis Molecular Biology of the Cell by :

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Toxicity, Uptake and Applications of Intracellular Delivery by Cell Penetrating Peptides

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Publisher :
ISBN 13 :
Total Pages : 107 pages
Book Rating : 4.:/5 (472 download)

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Book Synopsis Toxicity, Uptake and Applications of Intracellular Delivery by Cell Penetrating Peptides by : Gisela Tünnemann

Download or read book Toxicity, Uptake and Applications of Intracellular Delivery by Cell Penetrating Peptides written by Gisela Tünnemann and published by . This book was released on 2009 with total page 107 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Therapeutic Oligonucleotides

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Publisher : Royal Society of Chemistry
ISBN 13 : 0854041168
Total Pages : 362 pages
Book Rating : 4.8/5 (54 download)

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Book Synopsis Therapeutic Oligonucleotides by : Jens Kurreck

Download or read book Therapeutic Oligonucleotides written by Jens Kurreck and published by Royal Society of Chemistry. This book was released on 2008 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compelling overall update on current status of RNA interference

Intracellular Delivery of Functional Cargos Using Cell Penetrating Peptide Motifs

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Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (136 download)

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Book Synopsis Intracellular Delivery of Functional Cargos Using Cell Penetrating Peptide Motifs by : Heba Azmy Salim

Download or read book Intracellular Delivery of Functional Cargos Using Cell Penetrating Peptide Motifs written by Heba Azmy Salim and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biologics such as cyclic peptides, proteins, and nucleic acids are a class of therapeutics that have the ability to modulate diverse undruggable targets. Biologics can bind to flat and large surfaces involved in undruggable protein-protein interactions (PPIs) in comparable to small molecules. However, applications of biologics are restricted by their inefficient penetration to the cell membrane to reach their targets in the cytosol. Cell-penetrating peptides (CPPs) are short peptide sequences that can effectively deliver biologically active cargo into cells. This work is focused on utilizing cyclic CPPs as delivery tools for functional biologics including cyclic peptides and proteins targeting intracellular PPIs.

Cellular Drug Delivery

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Publisher : Springer Science & Business Media
ISBN 13 : 1592597459
Total Pages : 621 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Cellular Drug Delivery by : D. Robert Lu

Download or read book Cellular Drug Delivery written by D. Robert Lu and published by Springer Science & Business Media. This book was released on 2004-02-25 with total page 621 pages. Available in PDF, EPUB and Kindle. Book excerpt: An authoritative and up-to-date survey of the fundamental principles, and practice of drug delivery at the cellular level. On the principles side, the authors discuss the broad spectrum of cellular delivery, ranging from coverage of cell-mediated immunity, gene delivery, and protein targeting, to cellular drug transport, cellular drug permeability, and a variety of carrier system related to targeted drug delivery. On the practice side, the authors focus on technological developments in cellular drug delivery, including novel formulations for the delivery of DNA and antisense oligonucleotides ,as well as drug targeting with immunoglobulin formulations and antibody-mediated approaches.

Peptide Based Intracellular Delivery

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Publisher :
ISBN 13 :
Total Pages : 179 pages
Book Rating : 4.:/5 (12 download)

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Book Synopsis Peptide Based Intracellular Delivery by : Isaac Abrrey Monreal

Download or read book Peptide Based Intracellular Delivery written by Isaac Abrrey Monreal and published by . This book was released on 2016 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.