New Biodegradable Elastomers for Drug and Therapeutic Protein Delivery PDF Download

Author: Mohamed Abdel Fattah Shaker Mahmoud
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 0

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Author: Namita Roy Choudhury
Publisher: Royal Society of Chemistry
ISBN: 1839161027
Category : Science
Languages : en
Pages : 297

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Book Description
Elastomeric proteins are ubiquitous in nature, where they have evolved precise structures and properties that are necessary to perform specific biological roles and functions. This book emphasizes the impact of amino acid sequence on modulating protein structure, properties, and function. Examples include conformational ensemble dynamics, environmental responsiveness, self-assembly, physico-mechanical properties, morphology, and properties tailored for biomedical applications. This foundational framework is not only critical to advance scientific understanding and knowledge on elastomeric proteins but also enables the conceptualization, rational design, and development of biosynthetic elastomers and their analogous polypeptides for a variety of applications. Edited and contributed by pioneering researchers in the field, the book provides a timely overview of the materials, along with the synthesis techniques, the unique characteristics of elastomeric proteins, and biomedical and industrial applications. The book will provide a reference for graduate students and researchers interested in designing biomimetic proteins tailored for various functions.

Author: Katie Anna Black
Publisher:
ISBN:
Category :
Languages : en
Pages : 88

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Book Description
A focus of the field of biomaterials is to use directed design to create new materials which replicate and enhance the intricate functions of the human body. Nature's own building blocks, peptides, are an ideal material to create self-assembling biomaterials as they are biodegradable, relatively easy to synthesize, and can be designed with a wide array of functions. In this dissertation, self-assembling peptide materials were optimized for two important medical applications: regenerative medicine and drug delivery. Peptide amphiphiles (PAs), peptides conjugated to fatty acid tails, can self-assemble into both spherical micelles and worm-like micelles. PA worm-like micelles are of particular interest for regenerative medicine applications for their ability to form viscoelastic hydrogels at high concentration. Here we created PA hydrogel systems with active formation and stabilization triggers that are amenable to in situ gelation. Two different methods of in situ gel formation in PA systems were investigated, shear force and pH. Shear-induced formation of worm-like micelles is demonstrated in the PA termed C16-W3K. Before shearing, C16-W3K PAs form spherical micelles in solution and exhibit little to no viscoelasticity. As the solution is subjected to simple shear flow with increasing shear rate, spherical micelles form elongated worm-like micelles up to microns in length. In the C16-W3K PA system, shear force induced the change not only of the micelle structure but also of the peptide secondary structure simultaneously. Worm-like micelle formation was also demonstrated using pH modulation, in the PA termed C16GSH, which was designed with a branched peptide headgroup of histidine and serine amino acids. At low pH, the histidine side chains are protonated and hydrogen bonding does not occur, creating weakly elastic hydrogels. At pH 7.4, above the pKa of the histidine imidazole group, cooperative hydrogen bonding occurs, stabilizing the self-assembled worm-like micelles and creating a strong viscoelastic hydrogel. This unique architecture of C16GSH makes it possible to create hydrogels spanning a wide range of stiffness (0.1-10 kPa). C16GSH were optimized in vitro and in vivo for the application of peripheral nerve regeneration. Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. One strategy to enhance regeneration inside nerve guide conduits is to fill the conduits with a hydrogel to mimic the native extracellular matrix found in peripheral nerves. C16GSH hydrogels were compared to a commercially available collagen gel, which has been previously investigated as a nerve guide filler gel. Schwann cells, a cell type important in the peripheral nerve regenerative cascade, were able to spread, proliferate and migrate better on C16GSH gels in vitro when compared to cells seeded on collagen gels. Moreover, C16GSH gels were implanted subcutaneously in a murine model and were found to be biocompatible, degrade over time, and support angiogenesis without causing inflammation or a foreign body immune response. Taken together, these results help optimize and instruct the development of a new synthetic, hydrogel as a luminal filler for conduit-mediated peripheral nerve repair. In the second half of this dissertation, peptide based complex coacervates were optimized for delivery of protein therapeutics. Complex coacervation is a liquid-liquid phase separation based on the electrostatic association of two oppositely charged polymers in aqueous solution. Coacervation results in micron sized droplets of a dense polymer-rich phase (coacervate) which is separate from the dilute polymer-poor solution phase (aqueous phase). Complex coacervates based on synthetic polypeptides have many desirable features for therapeutic protein delivery. They can be synthetically produced, can be made to be biocompatible and biodegradable, and their formation can be tuned by a wide array of parameters. In this dissertation, a method to encapsulate proteins by complex coacervation using polypeptides is explored. Protein encapsulation with a model protein system: bovine serum albumin (BSA) was demonstrated. Rheological properties were studied to determine the viscoelasticity which may have implications for cell internalization. It was demonstrated that there is tradeoff between loading efficiency and total loading. Therefore, depending on the application, high loading capacity, up to 1:3 molar ratio of protein to polypeptide, or 100% loading of the protein can be achieved, depending on the process and cost of the protein which is often high. Encapsulated BSA retained its secondary structure when encapsulated and was released under conditions of low pH due to disassembly of the coacervate. Lastly, protein loaded coacervates were shown to be non-toxic in a cell viability assay. Polypeptide complex coacervates show promise at encapsulating proteins for therapeutic delivery, but it is difficult to control their size and stability to due dynamic rearrangement and coalescence. To control the size and stability of polypeptide coacervates, the crosslinker EDC was used to create a peptide bond between the amino acid side groups of poly(L-lysine) (PLys) and poly(D/L-glutamic acid) (PGlu). By changing the ratio of PGlu to PLys colloidal stability was achieved without the need for an additional excipient. Surface charge of the particles was also controlled by this method. Final particle size was controlled by both molecular weight and concentration of the polypeptides. A span of particle diameter from to 272nm to 1.3 μm was achieved. Lastly, stability at low pH, where non-crosslinked coacervates disassemble, was demonstrated. A simple and tunable method to control particle size, such as the one presented here provides a possible solution to a major limitation in the field of drug delivery, control of particle size.

Author: Glen S. Kwon
Publisher: CRC Press
ISBN: 9780824725327
Category : Medical
Languages : en
Pages : 680

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Book Description
Emphasizing four major classes of polymers for drug delivery-water-soluble polymers, hydrogels, biodegradable polymers, and polymer assemblies-this reference surveys efforts to adapt, modify, and tailor polymers for challenging molecules such as poorly water-soluble compounds, peptides/proteins, and plasmid DNA.

Author: Husam Mohammed Younes
Publisher:
ISBN:
Category : Polymeric drug delivery systems
Languages : en
Pages : 370

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Author: Sangamesh G. Kum bar
Publisher: Newnes
ISBN: 0123972906
Category : Technology & Engineering
Languages : en
Pages : 421

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Book Description
Polymers are important and attractive biomaterials for researchers and clinical applications due to the ease of tailoring their chemical, physical and biological properties for target devices. Due to this versatility they are rapidly replacing other classes of biomaterials such as ceramics or metals. As a result, the demand for biomedical polymers has grown exponentially and supports a diverse and highly monetized research community. Currently worth $1.2bn in 2009 (up from $650m in 2000), biomedical polymers are expected to achieve a CAGR of 9.8% until 2015, supporting a current research community of approximately 28,000+. Summarizing the main advances in biopolymer development of the last decades, this work systematically covers both the physical science and biomedical engineering of the multidisciplinary field. Coverage extends across synthesis, characterization, design consideration and biomedical applications. The work supports scientists researching the formulation of novel polymers with desirable physical, chemical, biological, biomechanical and degradation properties for specific targeted biomedical applications. - Combines chemistry, biology and engineering for expert and appropriate integration of design and engineering of polymeric biomaterials - Physical, chemical, biological, biomechanical and degradation properties alongside currently deployed clinical applications of specific biomaterials aids use as single source reference on field. - 15+ case studies provides in-depth analysis of currently used polymeric biomaterials, aiding design considerations for the future

Author: Alexandru Mihai Grumezescu
Publisher: William Andrew
ISBN: 0128166290
Category : Medical
Languages : en
Pages : 580

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Book Description
Nanomaterials for Drug Delivery and Therapy presents recent advances in the field of nanobiomaterials and their important applications in drug delivery, therapy and engineering. The book offers pharmaceutical perspectives, exploring the development of nanobiomaterials and their interaction with the human body. Chapters show how nanomaterials are used in treatments, including neurology, dentistry and cancer therapy. Authored by a range of contributors from global institutions, this book offers a broad, international perspective on how nanotechnology-based advances are leading to novel drug delivery and treatment solutions. It is a valuable research resource that will help both practicing medics and researchers in pharmaceutical science and nanomedicine learn more on how nanotechnology is improving treatments. Assesses the opportunities and challenges of nanotechnology-based drug delivery systems Explores how nanotechnology is being used to create more efficient drug delivery systems Discusses which nanomaterials make the best drug carriers

Author: Kishor Kumar Sadasivuni
Publisher: Springer
ISBN: 3030047415
Category : Technology & Engineering
Languages : en
Pages : 409

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Book Description
This book presents a thorough discussion of the physics, biology, chemistry and medicinal science behind a new and important area of materials science and engineering: polymer nanocomposites. The tremendous opportunities of polymer nanocomposites in the biomedical field arise from their multitude of applications and their ability to satisfy the vastly different functional requirements for each of these applications. In the biomedical field, a polymer nanocomposite system must meet certain design and functional criteria, including biocompatibility, biodegradability, mechanical properties, and, in some cases, aesthetic demands. The content of this book builds on what has been learnt in elementary courses about synthesising polymers, different nanoparticles, polymer composites, biomedical requirements, uses of polymer nanocomposites in medicine as well as medical devices and the major mechanisms involved during each application. The impact of hybrid nanofillers and synergistic composite mixtures which are used extensively or show promising outcomes in the biomedical field are also discussed. These novel materials vary from inorganic/ceramic-reinforced nanocomposites for mechanical property improvement to peptide-based nanomaterials, with the chemistry designed to render the entire material biocompatible.

Author: M. N. V. Ravi Kumar
Publisher: CRC Press
ISBN: 1315341166
Category : Medical
Languages : en
Pages : 401

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Book Description
In the quest for innovative drug delivery systems attempting to meet the unmet needs in pharmaceutical space, research has taken a much more complicated path that poses a significant challenge for translation. Despite the progress made with novel materials, polyesters still remain at the helm of drug delivery technologies. This book provides a single source of reference of polyester drug delivery systems that covers a broad spectrum of materials design, manufacturing techniques, and applications.

Author: Anya M Hillery
Publisher: CRC Press
ISBN: 1482217740
Category : Medical
Languages : en
Pages : 634

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Book Description
This book provides a comprehensive introduction to advanced drug delivery and targeting, covering their principles, current applications, and potential future developments. This edition has been updated to reflect significant trends and cutting-edge advances that have occurred since the first edition was published. All the original chapters have been retained, but the material therein has been updated. Eight new chapters have been added that deal with entirely new technologies and approaches. Features: Offers a comprehensive introduction to the fundamental concepts and underlying scientific principles of drug delivery and targeting Presents an in-depth analysis of the opportunities and obstacles afforded by the application of nanotechnologies for drug delivery and targeting Includes a revised and expanded section on the major epithelial routes of drug delivery currently under investigation Describes the most recent, emerging, and innovative technologies of drug delivery Provides real-life examples of the clinical translation of drug delivery technologies through the use of case studies Discusses the pertinent regulatory hurdles and safety issues of drug delivery and targeting systems—crucial considerations in order to achieve licensing approval for these new technologies