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Self-assembled Polymeric Nanoparticles for Targeted Delivery of Anticancer Drugs

Author : Meng Shi (d)
Publisher :
Page : 512 pages
File Size : 32,66 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.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

Author : Jennifer Logie
Publisher :
Page : pages
File Size : 16,20 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.

Polymer Nanoparticles for Nanomedicines

Author : Christine Vauthier
Publisher : Springer
Page : 649 pages
File Size : 45,52 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.

Functional Polymers for Nanomedicine

Author : Youqing Shen
Publisher : Royal Society of Chemistry
Page : 331 pages
File Size : 29,81 MB
Release : 2013
Category : Medical
ISBN : 1849736200

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A complete overview of the different strategies for designing polymers for targeted gene therapy and drug delivery for researchers in polymer science, nanotechnology and pharmacy.

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics

Author : Prashant Kesharwani
Publisher : Academic Press
Page : 434 pages
File Size : 45,82 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

Block Co-polymeric Nanocarriers: Design, Concept, and Therapeutic Applications

Author : Neeraj Mishra
Publisher : Springer Nature
Page : 440 pages
File Size : 50,67 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.

Polymer and Polymer-Hybrid Nanoparticles

Author : Stanislav Rangelov
Publisher : CRC Press
Page : 504 pages
File Size : 41,26 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.

Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications

Author : Abdel Salam Hamdy Makhlouf
Publisher : Woodhead Publishing
Page : 694 pages
File Size : 21,1 MB
Release : 2018-06-14
Category : Technology & Engineering
ISBN : 008101998X

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Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications, Volume One: Types and Triggers discusses, in detail, the recent trends in designing biodegradable and biocompatible single-responsive polymers and nanoparticles for safe drug delivery. Focusing on the most advanced materials and technologies, evaluation methods, and advanced synthesis techniques stimuli-responsive polymers, the book is an essential reference for scientists with an interest in drug delivery vehicles. Sections focus on innovation, development and the increased global demand for biodegradable and biocompatible responsive polymers and nanoparticles for safe drug delivery. Offers an in-depth look at the basic and fundamental aspects of alternative stimuli-responsive polymers, mechanisms, structure, synthesis and properties Provides a well-defined categorization for stimuli-responsive polymers for drug delivery based on different triggering mechanisms Discusses novel approaches and challenges for scaling up and commercialization of stimuli-responsive polymers

Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for Drug Delivery

Author : Prashant Kesharwani
Publisher : Elsevier
Page : 534 pages
File Size : 50,84 MB
Release : 2023-03-02
Category : Technology & Engineering
ISBN : 0323914314

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Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for Drug Delivery is a comprehensive guide to PLGA nanoparticles for targeting various diseases, covering principles, formation, characterization, applications, regulations and the latest advances. Sections introduce the fundamental aspects of PLGA nanoparticles for drug delivery, including properties, preparation methods, characterization, drug loading methods, and drug release mechanisms, along with a focus on applications. Application of PLGA nanoparticles for the treatment of cancer, inflammatory, cerebral, cardiovascular, and infectious diseases, as well as in regenerative medicine, photodynamic and photothermal therapy, and gene therapy, are all explained in detail. The final chapters explore recent advances and regulatory aspects. This book is a valuable resource for researchers and advanced students across nanomedicine, polymer science, bio-based materials, chemistry, biomedicine, biotechnology, and materials engineering, as well as for industrial scientists and R&D professionals with an interest in nanoparticles for drug delivery, pharmaceutical formulations and regulations, and development of innovative biodegradable materials. Presents the fundamentals of PLGA nanoparticles, including properties, preparation, characterization, and biofate and cellular interactions Provides in-depth coverage of a broad range of specific applications of PLGA nanoparticles across disease treatment, regenerative medicine and therapeutic areas Offers a methodical approach to PLGA nanoparticles in drug delivery that is supported by data tables, illustrative figures and flowcharts