[PDF] Design And Synthesis Of Self Assembled Polymeric Nanoparticles For Cancer Drug Delivery eBook

Author : Jennifer Logie
Publisher :
Page : pages
File Size : 40,53 MB
Release : 2017
Category :
ISBN :

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Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P(LA-co-TMCC)-g-PEG nanoparticles as an effective delivery vehicle for two chemotherapeutics, and presents approaches amenable to the delivery of many other clinically relevant hydrophobic drugs or drug combinations.

Author : Christine Vauthier
Publisher : Springer
Page : 649 pages
File Size : 26,42 MB
Release : 2017-01-07
Category : Medical
ISBN : 3319414216

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This volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.

Author : Meng Shi (d)
Publisher :
Page : 512 pages
File Size : 44,19 MB
Release : 2008
Category :
ISBN : 9780494580882

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Targeted delivery of drugs to specific regions of the body, or even to specific regions of the cell, promises enhanced drug efficacy and reduced systemic toxicity. By covalently coupling targeting ligands, the smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. The main goal of the project is to create a polymeric nanoparticle drug delivery system from synthesized biodegradable polymers and modify the polymeric nanoparticles using targeting antibodies for targeted delivery of anticancer drugs.A new biodegradable copolymer poly(2-methyl, 2-carboxy trimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan) was synthesized and characterized. The copolymers self-assembled into spherical nanoparticles in aqueous environments with the hydrodynamic diameters controlled over a broad size range. Immuno-polymeric nanoparticles were created by coupling maleimide-modified anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies to the self-assembled nanoparticles through Diels-Alder (DA) chemistry. This new coupling methodology was demonstrated to be relatively rapid, highly efficient and specific under mild conditions. In vitro studies showed that the immuno-nanoparticles bound specifically and efficiently with SKBR3 breast cancer cells that overexpress HER2 receptors.Anticancer drugs were incorporated into the immuno-nanoparticle system and the drug delivery via an antibody-mediated targeting mechanism was investigated in vitro. First, a protein anticancer drug, interleukin-2 (IL-2), was physically encapsulated through polymer-drug association. The IL-2 encapsulated anti-HER2 immuno-nanoparticles exhibited a cell-binding associated IL-2 release in the extracellular space upon binding with HER2-overexpressing SKBR3 breast cancer cells. Second, a small molecule hydrophobic drug, doxorubicin (DOX), was chemically conjugated on the nanoparticle surface after the antibody coupling, using the same DA chemistry. The novel formulation localized DOX in the cell nucleus of HER2-overexpressing SKBR3 breast cancer cells and remained the biological function of conjugated DOX. Compared to the nanoparticles bearing DOX or anti-HER2 antibody alone, the nanoparticles having a combination of DOX and anti-HER2 antibody exhibited the most significant cytotoxicity and specificity against SKBR3 cells relative to healthy HMEC-1 endothelial cells, demonstrating the potential of the DOX-immuno-nanoparticles as a novel platform for intracellular DOX delivery.This work provides a novel means for the delivery of combination immunotherapy/chemotherapy to more effectively treat certain malignancies.

Author : Stanislav Rangelov
Publisher : CRC Press
Page : 504 pages
File Size : 35,79 MB
Release : 2013-08-28
Category : Science
ISBN : 1439869073

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Polymeric and hybrid nanoparticles have received increased scientific interest in terms of basic research as well as commercial applications, promising a variety of uses for nanostructures in fields including bionanotechnology and medicine. Condensing the relevant research into a comprehensive reference, Polymer and Polymer-Hybrid Nanoparticles: From Synthesis to Biomedical Applications covers an array of topics from synthetic procedures and macromolecular design to possible biomedical applications of nanoparticles and materials based on original and unique polymers. The book presents a well-rounded picture of objects ranging from simple polymeric micelles to complex hybrid polymer-based nanostructures, detailing synthetic procedures, techniques for characterization and analysis, properties, and behavior in selective solvents and dispersions. Each chapter contains background and introductory information, summarizing generalities on the nanosystems being discussed. The chapters also describe representative works of experts and provide in-depth, focused discussions. The authors present current knowledge on the following topics: Designed synthesis of functional polymers Construction of block copolymer micellar and nonmicellar self-assembled structures Construction of organic–organic hybrid nanosized particles Construction of organic–inorganic hybrid nanoparticles and nanoassemblies The final chapter addresses biological applications of polymeric nanoparticles, including delivery of low-molecular-weight drugs, macromolecular drugs, imaging and diagnostics, and photodynamic therapy. Summarizing important developments in the field, the authors condense relevant research into a comprehensive resource.

Author : Omar Azzaroni
Publisher : John Wiley & Sons
Page : 1801 pages
File Size : 18,25 MB
Release : 2023-04-25
Category : Technology & Engineering
ISBN : 3527834052

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Supramolecular Nanotechnology Provides up-to-date coverage of both current knowledge and new developments in the dynamic and interdisciplinary field of supramolecular nanotechnology In recent years, supramolecular nanotechnology has revolutionized research in chemistry, physics, and materials science. These easily manipulated molecular units enable the synthesis of novel nanomaterials for use in a wide range of current and potential applications including electronics, sensors, drug delivery, and imaging. Supramolecular Nanotechnology presents a state-of-the-art overview of functional self-assembling nanomaterials based on organic and polymeric molecules. Featuring contributions by an international panel of experts in the field, this comprehensive volume covers the design of self-assembled materials, their synthesis and diverse fabrication methods, the characterization of supramolecular architectures, and current and emerging applications in chemistry, biology, and medicine. Detailed chapters discuss the synthesis of peptide-based supramolecular structures and polymeric self-assembling materials, their characterization, advanced microscopy techniques, nanostructures made of porphyrins, polyelectrolytes, silica, their application in catalysis and cancer, atomistic and coarse-grained simulations, and more. Presents cutting-edge research on rationally designed, self-assembled supramolecular structures Discusses the impact of supramolecular nanotechnology on current and future research and technology Highlights applications of self-assembled supramolecular systems in catalysis, biomedical imaging, cancer therapies, and regenerative medicine Provides synthetic strategies for preparing the molecular assemblies and various characterization techniques for assessing the supramolecular morphology Describes theoretical modeling and simulation techniques for analyzing supramolecular nanostructures Supramolecular Nanotechnology: Advanced Design of Self-Assembled Functional Materials is essential reading for materials scientists and engineers, polymer and organic chemists, pharmaceutical scientists, molecular physicists and biologists, and chemical engineers.

Author : Neeraj Mishra
Publisher : Springer Nature
Page : 440 pages
File Size : 50,15 MB
Release : 2023-11-29
Category : Medical
ISBN : 9819969174

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This book focuses on current advancements in the field of block copolymers and covers design, concept, and various therapeutic applications in the drug delivery. It also reviews the use of block copolymers in drug delivery applications from the development of sustained release products to smart polymeric delivery systems such as stimuli-responsive polymeric systems, for example, thermosensitive, redox-sensitive, photo-sensitive, and enzyme-sensitive. The book further discusses the nano assemblies from amphiphilic block copolymers as nanomedicine platforms for diagnosis and therapy due to their relatively small size, high drug loading capacity, controlled drug release, in vivo stability, and prolonged blood circulation. The chapters also review the various patents and ongoing clinical trials on the applications, covering several important new concepts and findings in the field of block copolymers. The book is aimed at researchers, academicians, and industrial scientists involved in the development of drug-delivery systems based on polymers.

Author : Prashant Kesharwani
Publisher : Academic Press
Page : 434 pages
File Size : 11,79 MB
Release : 2019-06-25
Category : Medical
ISBN : 0128173319

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Polymeric Nanoparticles as Promising Tool for Anti-cancer Therapeutics provides an understanding of polymeric compounds and their use in cancer therapies. The book begins by giving an overview of the current status, future challenges and potential utilization of polymeric nanoparticles. It then covers specific polymeric nanoparticles through contributions from world-renowned experts and researchers. Chapters examine specific polymeric nanoparticles, their development as potential targeted delivery systems, and cancer characteristics that can be targeted for therapy development. The book synthesizes current research trends in the field, thus enhancing existing knowledge of nanomedicine, drug delivery and therapeutic intervention strategies in human cancers. Users will find this to be an ideal reference for research scientists and those in the pharmaceutical and medical fields who are working to develop novel cancer therapies using nanoparticle-based delivery systems. Explores the development of polymeric nanoparticle systems for the purpose of cancer therapy Presents thoroughly analyzed data and results regarding the usage of polymeric nanoparticles-based platforms for the diagnosis and treatment of cancer Highlights various cancer characteristics that can be targeted for therapeutic development using polymeric nanoparticles

Author : Pedro Miguel Valencia
Publisher :
Page : 154 pages
File Size : 10,90 MB
Release : 2013
Category :
ISBN :

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The use of nanotechnology to engineer drug delivery vehicles comprised of controlled release polymers with targeting molecules has the potential to revolutionize cancer therapy, among other diseases. Although a myriad of nanotherapeutics have been developed at the bench side, many of them stay at the research stage due to their complexity and difficulty in their optimization. A key challenge for optimization of nanoparticles (NPs) for drug delivery is the ability to systematically and combinatorially create and screen libraries of NPs with distinct physicochemical properties, from which promising formulations can be moved forward to preclinical and clinical studies. In this work, the development of a controlled method to synthesize libraries of NPs with distinct properties is described. The procedure uses a microfluidic platform that rapidly mixes reagents and provides homogeneous reaction environments, resulting in the reproducible, single-step synthesis of NPs with well-defined properties and narrow size distributions. The microfluidic system is composed of a mixing unit and a NP assembly unit. The mixing unit consists of a multi-inlet, 2-layer mixer where different precursors such as polymers of different MW and charge, ligand- and drug-conjugated polymers, free drugs, and solvents are mixed at different ratios into a homogenous solution. In the assembly unit, the precursor solution is quickly mixed with an anti-solvent (i.e. water) using 3D hydrodynamic flow focusing where NPs self-assemble after complete mixing. With the microfluidic platform, a library of 100 NPs with different sizes (15-200nm), charge (-30 to +30mV), surface chemistry (i.e. PEG coverage), surface ligand density (0-2.5105 ligands/[mu]m2), and drug loading (0-5 w/w%) was producedd in a high-throughput manner by simply varying the flow ratios of precursors entering the system. This library was implemented for (i) screening for formulations (in vitro and in vivo) with optimal clinical properties for cancer treatment and (ii) deepening the understanding of how NP properties affect their biological behavior. The platform developed in this work would likely lead to better understanding of the design parameters for polymeric NPs and their smoother transition to the clinic.

Author : José A. Pomposo
Publisher : John Wiley & Sons
Page : 504 pages
File Size : 16,61 MB
Release : 2017-08-18
Category : Technology & Engineering
ISBN : 3527806393

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This first book on this important and emerging topic presents an overview of the very latest results obtained in single-chain polymer nanoparticles obtained by folding synthetic single polymer chains, painting a complete picture from synthesis via characterization to everyday applications. The initial chapters describe the synthetics methods as well as the molecular simulation of these nanoparticles, while subsequent chapters discuss the analytical techniques that are applied to characterize them, including size and structural characterization as well as scattering techniques. The final chapters are then devoted to the practical applications in nanomedicine, sensing, catalysis and several other uses, concluding with a look at the future for such nanoparticles. Essential reading for polymer and materials scientists, materials engineers, biochemists as well as environmental chemists.