The advent of highly sophisticated drugs designed to interfere with specific cellular functions has created the demand for "intelligent" carriers that can efficiently deliver therapeutic agents in response to a pathophysiogical condition. Nanoscale intelligent systems can maximize the efficacy of therapeutic treatments in numerous ways because they have the ability to rapidly detect and response to disease states directly at the site and sparing physiologically healthy cells and tissues, thereby improving a patient's quality of life. Nanoparticle fabrication has primarily relied on emulsions, self-assembly and micelles based methods which inherently generate polydisperse spherical particles with little control over particle geometry. Despite significant progress in such drug delivery systems, critical limitations remain in synthesizing nanocarriers with highly controllable architecture (size, shape or aspect ratio) that can, at the same time, impart response-sensitive release mechanisms. These parameters are essential for controlling the in-vivo transport, bio-distribution, and drug release mechanisms. The objective of my dissertation is to employ the nanofabrication technique Step and Flash Imprint Lithography (S-FIL) to synthesize stimuli-responsive nanocarriers of precise architectures and composition. Applying S-FIL technology, fabrication of nanocarriers of a variety of shapes and sizes (down to 36nm length scale) that are also environmentally responsive by incorporating enzymatically-degradable peptides into the nanocarrier hydrogel matrix, to provide triggered release of encapsulated therapeutic agents in response to specific pathophysiological conditions, has been accomplished. Besides disease-responsive release, the two key properties of an effective nanocarrier are (a) efficient targeting to specific tissues and cells and (b) avoiding rapid clearance and remaining in circulation in the blood stream for a significant amount of time to increase particle uptake in target tissues. These two properties are expected to be dependent on the shape and size of the carriers. Using various shape and size S-FIL fabricated nanoparticles, the effects of particle geometry on intracellular uptake has also been evaluated. In this dissertation, I will present the extensive work that has been done in the fabrication and optimization of the S-FIL nanocarriers, evaluation of the nanocarrier's in vitro properties, and evaluation of the effects of nanocarrier geometry on intracellular uptake.

Stimuli-Responsive Nanocarriers: Recent Advances in Tailor-Made Therapeutics compiles dispersed knowledge into a complete and comprehensive source to help researchers understand and progress stimuli-responsive nanocarriers. The book contains recent advancements made in the field of stimuli-responsive nanocarriers with their application in controlled drug delivery against various diseases. It focuses on the design, mechanism, construction, therapeutic application and future challenges of stimuli-responsive nanocarriers which will help new researchers in designing next generation tailor-made advanced therapeutics. Finally, the book covers future aspects and challenges present in the route of development of stimuli responsive nanocarriers for disease therapeutics. Various recent advances and biomedical applications assembled in this book will guide scientists on how to design and develop novel controlled drug release systems. - Provides comprehensive knowledge of basic design, mechanism and construction of nanocarrier based stimuli-responsive drug releases - Explores various nanocarriers characteristically used in the development of stimuli-responsive drug release systems - Envisages future opportunities, challenges and implementation of nanocarrier based stimuli-responsive drug release systems in disease therapeutics

Our ability to precisely manipulate size, shape, and composition of nanoscale carriers is essential for controlling their in-vivo transport, biodistribution, and drug release mechanism. Shape-specific, "smart" nanoparticles that deliver drugs or imaging agents to target tissues primarily in response to disease-specific or physiological signals could significantly improve therapeutic care of complex diseases. Current methods in nanoparticle synthesis do not allow such simultaneous control over particle size, shape, and environmentally-triggered drug release, especially at the sub-100 nm range. In this dissertation, we discuss the development of high-throughput nanofabrication techniques using synthetic and biological macromers (peptides) to produce highly monodisperse nanoparticles, as well as enzymatically-triggered nanoparticles, of precise sizes and shapes. We evaluated thermal nanoimprint lithography (ThNIL) and step and flash imprint lithography (SFIL) as two possible fabrication techniques. We successfully employed ThNIL and SFIL for fabricating nanoparticles and have extensively characterized the SFIL fabrication process, as well as the properties of the imprinted biopolymers. Particles as small as 50 nm were fabricated on silicon wafers and harvested directly into aqueous buffer using a biocompatible, one-step release technique. These methods provide a novel way to fabricate biocompatible nanoparticles with precise size and geometry. Furthermore, we developed an enzyme-degradable material system and demonstrated successful encapsulation and enzyme-triggered release of antibodies and nucleic acids from these imprinted nanoparticles; thus providing a potential means for disease-controlled delivery of biomolecules. Finally, we evaluated the bioactivity of the encapsulated therapeutics in-vitro. The development of the SFIL method for fabrication of biocompatible nanocarriers has great potential in the drug delivery field for its ability to create monodisperse particles of pre-designed geometry and size, and to incorporate stimulus-responsive release mechanisms. This research provides the potential to broaden the study of how particle size and shape affect the biodistribution of drugs within the body.

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

Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications: Volume Two: Advanced Nanocarriers for Therapeutics discusses, in detail, the recent trends in designing dual and multi-responsive polymers and nanoparticles for safe drug delivery. Chapters cover dual-responsive polymeric nanocarriers for drug delivery and their different stimuli, multi-responsive polymeric nanocarriers, and the therapeutic applications of stimuli-responsive polymers. With an emphasis on advanced medical applications and synergistic operational and technological methodologies for the improvement of polymers systems for the production of stimuli-responsive polymers, this book is essential reading for materials scientists and researchers working in the drug delivery and pharmaceutical industries. As innovation and development in the area of stimuli responsive polymer-based nanomaterials for drug delivery is moving fast and there is an increased global demand for biodegradable and biocompatible responsive polymers and nanoparticles for safe drug delivery, users will find this to be a timely resource. - Focusses on the most advanced technologies, recent evaluation methods, technical aspects, and advanced synthesis techniques stimuli-responsive polymers - Examines advanced medical applications of stimuli responsive polymers - Analyzes synergistic operational and technological methodologies for the improvement of polymer systems for the production of stimuli-responsive polymers in drug delivery

The increased understanding of molecular aspects associated with chronic diseases, such as cancer and the role of tumor microenvironment, has led to the identification of endogenous and exogenous stimuli that can be exploited to devise “stimuli-responsive” materials for site-specific drug delivery applications. This book provides a comprehensive account on the design, materials chemistry, and application aspects behind these novel stimuli-responsive materials. Setting the scene, the editors open with a chapter addressing the need for smart materials in delivery applications for therapy, imaging and disease diagnosis. The following chapter describes the key physical and chemical aspects of smart materials, from lipids to polymers to hybrid materials, providing the reader with a springboard to delve into the more application oriented chapters that follow. With in-depth coverage of key drug delivery systems such as pH-responsive, temperature responsive, enzyme-responsive and light responsive systems, this book provides a rigorous foundation to the field. A perfect resource for graduate students and newcomers, the closing chapter on regulatory and commercialization challenges also makes the book ideal for those wanting to take the next step towards clinical translation.

The concept of smart drug delivery vehicles involves designing and preparing a nanostructure (or microstructure) that can be loaded with a cargo. This can be a therapeutic drug, a contrast agent for imaging, or a nucleic acid for gene therapy. The nanocarrier serves to protect the cargo from degradation by enzymes in the body, to enhance the solubility of insoluble drugs, to extend the circulation half-life, and to enhance its penetration and accumulation at the target site. Importantly, smart nanocarriers can be designed to be responsive to a specific stimulus, so that the cargo is only released or activated when desired. In this volume we cover smart nanocarriers that respond to internal stimuli that are intrinsic to the target site. These stimuli are specific to the cell type, tissue or organ type, or to the disease state (cancer, infection, inflammation etc). pH-responsive nanostructures can be used for cargo release in acidic endosomal compartments, in the lower pH of tumors, and for specific oral delivery either to the stomach or intestine. Nanocarriers can be designed to be substrates of a wide-range of enzymes that are over-expressed at disease sites. Oxidation and reduction reactions can be taken advantage of in smart nanocarriers by judicious molecular design. Likewise, nanocarriers can be designed to respond to a range of specific biomolecules that may occur at the target site. In this volume we also cover dual and multi-responsive systems that combine stimuli that could be either internal or external.

The concept of smart drug delivery vehicles involves designing and preparing a nanostructure (or microstructure) that can be loaded with a cargo, this can be a therapeutic drug, a contrast agent for imaging, or a nucleic acid for gene therapy. The nanocarrier serves to protect the cargo from degradation by enzymes in the body, to enhance the solubility of insoluble drugs, to extend the circulation half-life, and to enhance its penetration and accumulation at the target site. Importantly, smart nanocarriers can be designed to be responsive to a specific stimulus, so that the cargo is only released or activated when desired. In this volume we cover smart nanocarriers that respond to externally applied stimuli that usually involve application of physical energy. This physical energy can be applied from outside the body and can either cause cargo release, or can activate the nanostructure to be cytotoxic, or both. The stimuli covered include light of various wavelengths (ultraviolet, visible or infrared), temperature (increased or decreased), magnetic fields (used to externally manipulate nanostructures and to activate them), ultrasound, and electrical and mechanical forces. Finally we discuss the issue of nanotoxicology and the future scope of the field.

Stimuli-Responsive Nanocarriers for Targeted Drug Delivery presents a comprehensive overview of the most significant physical and chemical stimuli-responsive drug delivery systems. This book reviews targeted and controlled drug delivery systems and how nanocarriers can be used to improve the pharmacokinetics of drugs in biological systems, such as increasing utilization rate and reducing toxicity and side effects. After a key introduction to the topic, a range of nanocarrier types is assessed before exploring the clinical translation challenges and considerations involved.This book is a useful resource for researchers and postgraduate students in the fields of materials science, nanotechnology, pharmaceutical science, and medicinal chemistry. - Offers an in-depth look at the basic and fundamental aspects of stimuli-responsive materials, mechanisms, structure, synthesis and properties - Provides information about well-defined categorization for stimuli-responsive drug delivery system based on different triggering mechanisms to its reader - Reviews basic concepts and the latest research involving advances in stimuli-responsive drug delivery systems in controlled-release drugs - Discusses novel approaches and challenges for scaling-up and commercialization of stimuli-responsive polymers

Drug Targeting and Stimuli Sensitive Drug Delivery Systems covers recent advances in the area of stimuli sensitive drug delivery systems, providing an up-to-date overview of the physical, chemical, biological and multistimuli-responsive nanosystems. In addition, the book presents an analysis of clinical status for different types of nanoplatforms. Written by an internationally diverse group of researchers, it is an important reference resource for both biomaterials scientists and those working in the pharmaceutical industry who are looking to help create more effective drug delivery systems. Shows how the use of nanomaterials can help target a drug to specific tissues and cells Explores the development of stimuli-responsive drug delivery systems Includes case studies to showcase how stimuli responsive nanosystems are used in a variety of therapies, including camptothecin delivery, diabetes and cancer therapy