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Physicochemical and Biological Characterization of Degradable Polyelectrolyte Multilayers for Surface-mediated DNA Delivery

Physicochemical and Biological Characterization of Degradable Polyelectrolyte Multilayers for Surface-mediated DNA Delivery PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
The work described in this thesis focuses on the evaluation of synthetic organic materials to either (i) mediate the delivery of DNA from thin polymer films on surfaces or (ii) create functional coatings on surfaces with potential biomedical applications related to drug delivery and cell adhesion. In both cases, layer-by-layer fabrication was used to assemble films on surfaces through the iterative immersion of substrates in alternating solutions of complementary functionality (e.g. alternating solutions of polycations and polyanions or alternating solutions of organic materials possessing nucleophilic or electrophilic functional groups in order to create polyelectrolyte and covalent multilayers, respectively). The DNA-related studies build upon previous work demonstrating that films fabricated using a hydrolytically degradable cationic polymer can release DNA over a period of one to two days and promote transgene expression both in vitro and in vivo. Chapter 2 reports the synthesis of a fluorescently end-labeled degradable cationic polymer and its application to characterize the erosion of polyelectrolyte multilayers fabricated using a model polyanion. Chapter 3 used this fluorescently labeled cationic polymer to provide more direct insight into fundamental interactions between the polymer and DNA during release from films and during trafficking by cells in vitro. The results of this chapter suggest that the polymer components of these films can play a role in promoting cellular uptake and trafficking of DNA. Chapter 4 characterized the application of this DNA-containing film system to deliver DNA encoding a potential therapeutic protein to investigate the extent to which this method of delivery could be used to reduce intimal hyperplasia in arterial tissue of rats after balloon-mediated injury. The results of this study provide guidance for the development of degradable polyelectrolyte multilayered thin films for the surface-mediated delivery of DNA. Chapter 5 demonstrated layer-by-layer fabrication of covalent films using a branched polyamine and small molecule pentacrylate to yield films possessing hydrolytically degradable ester bonds. These films were subsequently functionalized using unreacted acrylate groups to control film hydrophobicity and cell adhesion and provided a platform for the release of covalently attached molecules upon incubation in aqueous media.

Physicochemical and Biological Characterization of Degradable Polyelectrolyte Multilayers for Surface-mediated DNA Delivery

Physicochemical and Biological Characterization of Degradable Polyelectrolyte Multilayers for Surface-mediated DNA Delivery PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
The work described in this thesis focuses on the evaluation of synthetic organic materials to either (i) mediate the delivery of DNA from thin polymer films on surfaces or (ii) create functional coatings on surfaces with potential biomedical applications related to drug delivery and cell adhesion. In both cases, layer-by-layer fabrication was used to assemble films on surfaces through the iterative immersion of substrates in alternating solutions of complementary functionality (e.g. alternating solutions of polycations and polyanions or alternating solutions of organic materials possessing nucleophilic or electrophilic functional groups in order to create polyelectrolyte and covalent multilayers, respectively). The DNA-related studies build upon previous work demonstrating that films fabricated using a hydrolytically degradable cationic polymer can release DNA over a period of one to two days and promote transgene expression both in vitro and in vivo. Chapter 2 reports the synthesis of a fluorescently end-labeled degradable cationic polymer and its application to characterize the erosion of polyelectrolyte multilayers fabricated using a model polyanion. Chapter 3 used this fluorescently labeled cationic polymer to provide more direct insight into fundamental interactions between the polymer and DNA during release from films and during trafficking by cells in vitro. The results of this chapter suggest that the polymer components of these films can play a role in promoting cellular uptake and trafficking of DNA. Chapter 4 characterized the application of this DNA-containing film system to deliver DNA encoding a potential therapeutic protein to investigate the extent to which this method of delivery could be used to reduce intimal hyperplasia in arterial tissue of rats after balloon-mediated injury. The results of this study provide guidance for the development of degradable polyelectrolyte multilayered thin films for the surface-mediated delivery of DNA. Chapter 5 demonstrated layer-by-layer fabrication of covalent films using a branched polyamine and small molecule pentacrylate to yield films possessing hydrolytically degradable ester bonds. These films were subsequently functionalized using unreacted acrylate groups to control film hydrophobicity and cell adhesion and provided a platform for the release of covalently attached molecules upon incubation in aqueous media.

Surface-mediated Release and Transfer of Plasmid DNA Using Polyelectrolyte Multilayer Coatings

Surface-mediated Release and Transfer of Plasmid DNA Using Polyelectrolyte Multilayer Coatings PDF Author: Visham Appadoo
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
The work described in this thesis focuses on (i) the development of materials and approaches for the surface-mediated gene delivery using DNA-containing polyelectrolyte films, and (ii) the design of covalently-bonded hydrolytically degradable assemblies fabricated using PVDMA-based polymers. The work in the first section was built upon several past reports from our group on the design of thin films for delivery of DNA in vitro and in vivo, on a wide range of timescales. These materials have the potential to be useful in therapeutic contexts and as tools in biomedical research. Specifically, the work reported here investigates polyelectrolyte multilayers fabricated using layer-by-layer assembly processes driven by intermolecular interactions. The first section describes the design and characterization of thin films that release plasmid DNA linearly over a period of 2-3 months in solution. At the other extreme of timescales, we sought to develop materials that could release DNA into solution or transfer DNA to soft hydrogel surfaces and soft animal tissue at short sub-minute durations. Rapid film disruption was induced by layers of poly(acrylic acid), a weak polyelectrolyte, when the pH was changed. Design principles for rapid contact transfer of DNA to soft surfaces were developed for films fabricated using degradable and non-degradable polyamines. We also designed and characterized an alternate platform for contact transfer that relied on rapidly erodible, sacrificial hydrogen-bonded multilayers to 'release' the DNA-containing films to solution or to a secondary surface. In each case, selected coatings were fabricated on the surfaces of inflatable balloon catheters and investigated in vivo using rat and pig animal models. The second section was focused on novel covalently crosslinked soft material assemblies (films, gels, and capsules) that were hydrolytically degradable in aqueous environments. Azlactone-based covalently crosslinked soft materials were designed to be hydrolytically degradable through the cleavage of ester or acetal linkages. The materials could also be modified post-fabrication using different primary amines, in ways that could be used to tune their physicochemical properties.

Surface-mediated Gene Delivery Using DNA-containing Multilayered Polyelectrolyte Films

Surface-mediated Gene Delivery Using DNA-containing Multilayered Polyelectrolyte Films PDF Author: Eric M. Saurer
Publisher:
ISBN:
Category :
Languages : en
Pages : 202

Book Description


Polyelectrolytes

Polyelectrolytes PDF Author: Visakh P. M.
Publisher: Springer
ISBN: 3319016806
Category : Technology & Engineering
Languages : en
Pages : 388

Book Description
This book offers a valuable reference source to graduate and post graduate students, engineering students, research scholars polymer engineers from industry. The book provides the reader with current developments of theoretical models describing the thermodynamics polyelectrolytes as well as experimental findings. A particular emphasis is put on the rheological description of polyelectrolyte solutions and hydrogels.

Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents

Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents PDF Author: Manju Rawat Singh
Publisher: Academic Press
ISBN: 0128199180
Category : Business & Economics
Languages : en
Pages : 657

Book Description
Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents provides sound data on the utility of biological and plant-based drugs and describes challenges faced in all aspects offering indispensable strategies to use in the development of bioactive medicines. Bioactive based medications are commonly used throughout the world and have been recognized by physicians and patients for their therapeutic efficacy. Bioactive formulations, including their subordinates and analogs, address 50% of all medicines in clinical practice. Novel bioactive medicine transporters can cure many disorders by both spatial and transitory approaches and have various justifications in medicinal potential. This book presents information on the utility of natural, plant, animal and bioengineered bioactive materials. It is a fundamental source of information and data for pharmacognosists, pharmaceutical analysts, drug transport scientists and pharmacologists working in bioactive medications. Advances information on various bioactive based medications, their sources, clinical consequences and transport strategies Illustrates diverse transport systems for bioactives and derivatives, novel techniques for formulations, targeting strategies and fundamental qualities of developed bioactive carriers, and their safety concerns and standardization Discusses distinctive transport systems, stability, upgraded dissolvability, and enhanced bioavailability of bioactives

Thin Films and Coatings in Biology

Thin Films and Coatings in Biology PDF Author: Soroush Nazarpour
Publisher: Springer Science & Business Media
ISBN: 9400725922
Category : Science
Languages : en
Pages : 367

Book Description
The surface of materials is routinely exposed to various environmental influences. Surface modification presents a technological challenge for material scientists, physicists, and engineers, particularly when those surfaces are subjected to function within human body environment. This book provides a comprehensive coverage of the major issues and topics dealing with interaction of soft living matter with the surface of implants. Fundamental scientific concepts are embedded through experimental data and a broad range of case studies. First chapters cover the basics on biocompatibility of many different thin films of metals, alloys, ceramics, hydrogels, and polymers, following with case studies dealing with orthopedic and dental coatings. Next, a novel and low-cost coating deposition technique capable of production of several types of nanostructures is introduced through simple calculations and several illustrations. Moreover, chapter 6 and 7 present important topics on surface treatment of polymers, which is a subject that has seen many developments over the past decade. The last chapters target mainly the applications of coatings in biology such as in bio-sensing, neuroscience, and cancer detection. With several illustrations, micrographs, and case studies along with suitable references in each chapter, this book will be essential for graduate students and researchers in the multidisciplinary field of bio-coatings.

Biomimetic Polymers

Biomimetic Polymers PDF Author: C.G. Gebelein
Publisher: Springer Science & Business Media
ISBN: 1461306574
Category : Science
Languages : en
Pages : 297

Book Description
The term biomimetic is comparatively new on the chemical scene, but the concept has been utilized by chemists for many years. Furthermore, the basic idea of making a synthetic material that can imitate the func tions of natural materials probably could be traced back into antiquity. From the dawn of creation, people have probably attempted to duplicate or modify the activities of the natural world. (One can even find allusions to these attempts in the Bible; e. g. , Genesis 30. ) The term "mimetic" means to imitate or mimic. The word "mimic" means to copy closely, or to imitate accurately. Biomimetic, which has not yet entered most dictionaries, means to imitate or mimic some specific bio logical function. Usually, the objective of biomimetics is to form some useful material without the need of utilizing living systems. In a simi lar manner, the term biomimetic polymers means creating synthetic poly mers which imitate the activity of natural bioactive polymers. This is a major advance in polymer chemistry because the natural bioactive polymers are the basis of life itself. Thus, biomimetic polymers imitate the life process in many ways. This present volume delineates some of the recent progress being made in this vast field of biomimetic polymers. Chemists have been making biomimetic polymers for more than fifty years, although this term wasn't used in the early investigations.

Polymer Capsules

Polymer Capsules PDF Author: Ye Liu
Publisher: CRC Press
ISBN: 0429767870
Category : Science
Languages : en
Pages : 385

Book Description
Polymers are one of the most versatile and important materials used for capsule preparation despite various others available. Suitably formulated capsules can securely protect ingredients, deliver them to targeted sites, and release them expeditiously, improving functions and minimizing adverse effects. New polymers are constantly being explored to develop more efficient capsules as they are routinely used in pharmaceuticals, consumer healthcare products, nutrients, and food. This book focuses on the current state of the art of polymer-based capsules and delivery systems. It describes the formulation processes of capsules developed from redox-responsive polymers and polymer-functionalized carbon nanotubes, in addition to shedding light on coacervation of polymers for encapsulation. It reviews different active ingredients that can be used with polymer capsules in various products, encapsulation of essential oils using such capsules, and development of polymer capsules of cells and bacteriophages.

Smart Nanocontainers

Smart Nanocontainers PDF Author: Phuong Nguyen Tri
Publisher: Elsevier
ISBN: 0128168919
Category : Technology & Engineering
Languages : en
Pages : 558

Book Description
Smart Nanocontainers explores the fundamental concepts and emerging applications of nanocontainers in biomedicine, pharmaceuticals and smart materials. In pharmaceuticals, nanocontainers have advantages over their micro-counterparts, including more efficient drug detoxification, higher intracellular uptake, better stability, less side effects and higher biocompatibility with tissue and cells. In materials science, such as coating technology, they help by making coatings smarter, stronger and more durable. This important reference will help anyone who wants to learn more on how nanocontainers are used to provide the controlled release of active agents, including their applications in smart coatings, corrosion, drug delivery, diagnosis, agri-food and gas storage. Discusses how the molecular design of nanocarriers can be optimized to increase performance Explores how nanocarriers are being used to produce a new generation of active coatings Explains how nanocarriers are being used to deliver more effective nanoscale drug delivery

Nanocarrier Technologies

Nanocarrier Technologies PDF Author: M. Reza Mozafari
Publisher: Springer Science & Business Media
ISBN: 1402050410
Category : Medical
Languages : en
Pages : 238

Book Description
Designed as an advanced survey of the field, this book describes the key research parameters of nanocarrier technologies. It is the first book with this topic. It comprises a collection of scientific articles from top research people in the field and provides an up-to-date source containing recent citation and bibliography. The book is an indispensable source of information for new researchers and scientists.