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Nanoparticles are emerging as carriers in biological applications due to advances in their preparation, size control, surface modification and encapsulation capabilities. In addition, nanomaterials improve bioavailability by enhancing aqueous solubility of the guest molecule and increasing resistance time in the body. However, the delivery of guest molecules is still challenging due to the intrinsic characteristics of the guest molecule including large size and propensity to denature or degradation in the case of biomolecules and the encapsulation stability of the small guest molecules. Our group recently reported the preparation of self-cross-linked polymeric nanogels possessing surface functionalization capabilities. In this dissertation we employed the use of polymeric nanogels to explore and understand their guest encapsulation capabilities with both hydrophilic and hydrophobic molecules. We were able to encapsulate a protein in the hydrophobic core of the nanogels and recover is enzymatic activity upon release. Moreover the surface of these nanogels can be also decorated with surface exposed cysteine containing protein. We also reported a straightforward methodology for the preparation of tri-functionalized amine materials with high functional density.
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.
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.
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.
This important new book provides the fundamental understanding of the peptide and protein drug delivery systems with a special focus on their nanotechnology applications. Addressing an increasing interest in peptide and protein drug delivery systems in both academic and industrial circles worldwide, this book fills the need for a comprehensive review and assessment of conventional and nonconventional routes of administration.
There is a clear need for innovative technologies to improve the delivery of therapeutic and diagnostic agents in the body. Recent breakthroughs in nanomedicine are now making it possible to deliver drugs and therapeutic proteins to local areas of disease or tumors to maximize clinical benefit while limiting unwanted side effects. Nanomedicine in Drug Delivery gives an overview of aspects of nanomedicine to help readers design and develop novel drug delivery systems and devices that build on nanoscale technologies. Featuring contributions by leading researchers from around the world, the book examines: The integration of nanoparticles with therapeutic agents The synthesis and characterization of nanoencapsulated drug particles Targeted pulmonary nanomedicine delivery using inhalation aerosols The use of biological systems—bacteria, cells, viruses, and virus-like particles—as carriers to deliver nanoparticles Nanodermatology and the role of nanotechnology in the diagnosis and treatment of skin disease Nanoparticles for the delivery of small molecules, such as for gene and vaccine delivery The use of nanotechnologies to modulate and modify wound healing Nanoparticles in bioimaging, including magnetic resonance, computed tomography, and molecular imaging Nanoparticles to enhance the efficiency of existing anticancer drugs The development of nanoparticle formulations Nanoparticles for ocular drug delivery Nanoparticle toxicity, including routes of exposure and mechanisms of toxicity The use of animal and cellular models in nanoparticles safety studies With its practical focus on the design, synthesis, and application of nanomedicine in drug delivery, this book is a valuable resource for clinical researchers and anyone working to tackle the challenges of delivering drugs in a more targeted and efficient manner. It explores a wide range of promising approaches for the diagnosis and treatment of diseases using cutting-edge nanotechnologies.
Over the last few decades, numerous nanoparticle platforms have been studied for their use in therapeutic applications. This book deals with the description of the construction of technical systems that combines different functionalities which bring liposomes, polymer-drug conjugates, polymer-protein conjugates, dendrimers, polymeric micelles, polymerosomes and other nanoparticles into the realm of nanotechnology proper, as opposed to traditional pharmacology or supramolecular chemistry. The volume additionally covers topics such as passive and active targeting, the strategies used for drug targeting, and the synthesis and characterization of polymeric nanoparticle platforms. Targeted polymeric nanomedicines have shown exciting results in preclinical studies, demonstrating their potential as therapeutic carriers. Therefore, the development of polymeric nanomedicines as therapeutic agents has generated great enthusiasm both in academia and industry. The book is systematically divided into chapters devoted to a class of polymeric nanomedicines. Each chapter also describes relevant aspects relating to drug design and targeting of polymeric nanomedicines wherever possible. In addition, a series of chapters concerning the contribution of polymeric nanomedicines in the treatment of several categories of diseases including cancer, inflammatory, renal, immunological diseases, and brain disorders is also presented. Key features of this book include: - A comprehensive and cutting-edge overview of polymeric nanomedicines available in a single dedicated volume - Discussions on advances in drug delivery systems for a variety of diseases - more than 2000 references, tables, equations, and drawings Readers, whether beginners or experts, will find in this book, contemporary and relevant information regarding the synthesis, evaluation and applications of polymeric nanomedicines. Supplemented with extensive bibliographic references, tables and figures, this book is an essential and incomparable reference for medicinal chemists, biologists, and medical (oncologic) researchers, as well as for scientists, undergraduate and graduate students in the field of medical bioengineering and polymer nanoscience.
This book presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles.
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.