The recent introduction of nanomedicines in the drug therapy arena is revolutionizing the management of severe diseases. The key advance in the field is the optimization of the biological fate of drug molecules, thus improving the therapeutic effect while keeping to a very minimum the associated toxicity. Volume one of this book series, Nanoplatforms in Drug Delivery, established the basic aspects in the development of drug-loaded nanoplatforms, the so-called nanomedicines or nanodrugs, focusing on representative materials and strategies used in their formulation. Taking advantage of the advanced conceptualizations on nanomedicine engineering that were described in volume one, volume two, Nano-Engineering Strategies and Nanomedicines against Severe Diseases, analyzes in depth special features related to the formulation of nanoplatforms for oral, dental, topical and transdermal, pulmonary and nasal, ocular and otic, vaginal, and brain drug delivery and targeting. Particular aspects of nanomedicine engineering and in vivo fate associated with the routing of drug administration are given special attention. In addition, an up-to-date view is presented on the use of nanomedicines against severe diseases, such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious diseases, chronic inflammatory diseases, and metabolic diseases. The chapters analyze the key factors that need to be controlled to achieve the optimum therapeutic effect. Attention is further given to gene delivery and the recent concept of nanotheranosis.

This volume, the first of the two-volume Drug Delivery Approaches and Nanosystems series, presents a full picture of the state-of-the-art research and development in drug delivery systems using nanotechnology and its applications. It addresses the ever-expanding application of nanotechnology or nano-sized materials in the medical field and the real-world challenges and complexities of current drug delivery methodologies and techniques. Many methods of drug delivery systems have been used, but very few of them have been validated for medical use. A major reason for the above situation, the editors believe, is the gap between academia and research, and the gap between academic research and real-time clinical applications and needs. This volume addresses that gap. This volume presents 12 chapters that provide information about the preparation and characterization of nanocomposite materials used in drug delivery systems; advanced research of carbon nanotubes, nanocomposite materials, and polymer-clay, ceramics, and silicate glass-based nanocomposites; and the functionality of graphene nanocomposites. The book also provides detailed information on the application of nanotechnology in drug delivery systems in health care systems and medicine. The book describes how nanostructures are synthesized and draws attention to wide variety of nanostructures available for biological research and treatment applications. This valuable volume provides a wealth of information that will be valuable to scientists and researchers, faculty, and students. Volume 2 of the two-volume series is subtitled Drug Targeting Aspects of Nanotechnology. The volumes are available separately or as a set.

This volume is a thorough presentation of the state-of-the-art research and developments in drug delivery systems using nanotechnology and its applications. The second of this two-volume set, it addresses the applications of nanotechnology or nano-sized materials in the medical field and the real-world challenges and complexities of current drug delivery methodologies and techniques. This volume includes 11 chapters that focus on the targeting facet of drug delivery systems. Targeting is a focused maneuver to achieve the specified goals, including achieving the desired result and reaching the specific location. Targeting has now been successfully achieved for several diseases/disorders; however, its role is noteworthy in cancer treatment where chemotherapy is a main course of approach. Nanotechnology-based products have great potential by virtue of their inherent features. This edited book provides a detailed application of nanotechnology in drug delivery systems in health care. The book discusses general principles of drug targeting, material of construction and technological concerns of nanoparticles, and different drug delivery systems and their preparation. Taken together, the informative chapters will provide researchers and scientists as well as faculty and students with valuable research on the effective use of new approaches in advanced drug delivery nanosystems. Volume 1 of the two-volume series is subtitled Novel Drug Carriers. The volumes are available separately or as a set.

With chapters from highly skilled, experienced, and renowned scientists and researchers from around the globe, Dendrimers for Drug Delivery provides an abundance of information on dendrimers and their applications in the field of drug delivery. The volume begins with an introduction to dendrimers, summarizing dendrimer applications and the striking features of dendrimers. It goes on to present the details of usual properties, structure, classification, and methods of synthesis, with relevant examples. The toxicity of dendrimers is also discussed. The chapter authors provide an exhaustive amount of information about dendrimers and their biomedical applications, including biocompatibility and toxicity aspects, a very useful feature. This informative volume will be valuable resource that will help readers to create products derived from dendrimers and navigate through the regulatory, manufacturing, and quality control hurdles. It will be an important resource for researchers, scientists, upper-level students, and industry professionals.

Focusing on nanoparticulate nanocarriers and recent advances in the field of drug delivery, the volume begins with chapters that provide an informative introduction to polymeric nanoparticles-their general physicochemical features and characteristics, their applications in drug delivery systems, and the challenges involved. Specific applications are discussed, with attention paid to treatment of particular diseases and disorders and the targeting of specific organs. Part 2 looks at more specific applications and techniques of nanoparticulate nanocarriers for drug delivery, such as the use of magnetic nanoparticles, gold nanoparticles in therapeutics, and superparamagnetic iron oxide nanoparticles (SPIONs) for the treatment of cancer. Part 3 discusses lipid-based nanoparticulates for various applications, including skin care. The last section of the book explores some of the newer nanoarchitectures, including dendrimers in gene delivery and carbon nanotubes for drug delivery. Together, the insightful research presented here provides valuable information for those involved in this area, including scientists and researchers and faculty and upper-level students, as well as for industry professionals.

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.

This new volume focuses on the ever-growing and ever-sophisticated use of nanobiomaterials in drug delivery. There have been significant developments in the delivery of the active pharmaceutical ingredients to target sites, thereby sparing the normal functioning biological systems from damage, and this volume highlights some of the most important developments in the field. The book first provides an overview of nanobiomaterials and then goes on to report on new developments in drug delivery and nanotechnology, nanobiomaterials as carriers in cancer therapy, and the diverse uses of nanobiomaterials. Broken into sections, the chapters cover: an overview of nanobiomaterials drug delivery and nanotechnology nanobiomaterials as carriers in cancer therapeutics diverse uses of nanobiomaterials This volume will be a valuable resource on drug delivery for pharmaceutical manufacturers, healthcare personnel, and researchers.

This valuable new book, Handbook of Research on Medicinal Chemistry: Innovations and Methodologies, presents some of the latest advancements in the various fields of combinatorial chemistry, drug discovery, biochemical aspects, pharmacology of medicinal agents, current practical problems, and nutraceuticals. The editors keep the drug molecule as the central component of the volume and aim to explain the associated features essential to exhibiting pharmacological activity. With a unique combination of chapters in biology, clinical aspects, biochemistry, synthetic chemistry, medicine and technology, the volume provides broad exposure to the essential aspect of pharmaceuticals. The volume many important aspects of medicinal chemistry, including techniques in drug discovery pharmacological aspects of natural products chemical mediators: druggable targets advances in medicinal chemistry The field of medicinal chemistry is growing at an unprecedented pace, and this volume takes an interdisciplinary approach, covering a range of new research and new practices in the field. The volume takes into account the latest therapeutic guidelines put forward by the World Health Organization and the U.S Food and Drug Administration.. Topics include: drug design drug discovery natural products and supplements and nutraceuticals pharmaceutical approaches to sexual dysfunction drug resistance parasites new natural compounds and identification of new targets stereochemistry aspects in medicinal chemistry common drug interactions in daily practices Handbook of Research on Medicinal Chemistry: Innovations and Methodologies will be a valuable addition to the bookshelves of pharmaceutical scientists and faculty as well as for industry professionals.

Dendrimers, hyperbranched macromolecules, emerged just few decades ago but show promising potential as drug delivery nanocarriers, theranostic agents and gene vectors; in the pharmaceutical research and innovation area as well as in other healthcare applications. Although tremendous advancements have been made in dendrimer chemistry and their applications since their emergence, the synthesis, development and design of pure and safe dendrimer-based products have been a major challenge in this area. This book, edited by well-known researchers in the area of nanomaterials and drug-based drug delivery applications, exhaustively covers the nanotechnological aspects, concepts, properties, characterisation, application, biofate and regulatory aspects of dendrimers. It includes sixteen vivid chapters by renowned formulators, researchers and academicians from all over the world, highlighting their specialised areas of interest in the fields of chemistry, biology, pharmacy and nanomedicine. Features: * Highlights dendrimers' advancements in nanomedicine in the development of safe healthcare and biotechnological products * Covers physicochemical aspects, biofate, drug delivery aspects and gene therapy using dendrimers * Covers biomedical application of dendrimers in the field of biological sciences * Gives examples of dendrimer-guest interaction chemistry Dendrimers in Nanomedicine: Concept, Theory and Regulatory Perspectives provides the comprehensive overview of the latest research efforts in designing, optimising, development and scale-up of dendrimer-mediated delivery systems. It analyses the key challenges of synthesis, design, molecular modelling, fundamental concepts, drug delivery aspects, analytical tools and biological fate as well as regulatory consideration to the practical use of dendrimer application. Dr. Neelesh Kumar Mehra Assistant Professor of Pharmaceutics in the Department of Pharmaceutics at the National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, India. He has authored more than sixty peer-reviewed publications in highly reputed international journals, as well as book chapters and contributions on two patents. Dr. Mehra has 11 years of rich research and teaching experience in the formulation and development of complex, innovative biopharmaceutical products including micro- and nanotechnologies for regulated markets. Dr. Keerti Jain Assistant Professor of Pharmaceutics in the Department of Pharmaceutics, NIPER, Raebareli, India. For more than 10 years, she has been actively engaged in formulation and development of nanomedicines. Dr. Jain has supervised masters and doctoral pharmaceutics students in their research works which have been published in high quality, good impact factor journals. She has also authored more than 60 international manuscripts in peer reviewed high impact journals. In 2019, she was awarded the prestigious ICMR-Amir Shakuntala Award.

As with all of pharmaceutical production, the regulatory environment for the production of therapeutics has been changing as a direct result of the US FDA-initiated Quality by Design (QbD) guidelines and corresponding activities of the International Committee for Harmonization (ICH). Given the rapid growth in the biopharmaceutical area and the complexity of the molecules, the optimum use of which are still being developed, there is a great need for flexible and proactive teams in order to satisfy the regulatory requirements during process development. Process Analytical Technologies (PAT) applied in biopharmaceutical process development and manufacturing have received significant attention in recent years as an enabler to the QbD paradigm. PAT Applied in Biopharmaceutical Process Development and Manufacturing covers technological advances in measurement sciences, data acquisition, monitoring, and control. Technical leaders present real-life case studies in areas including measuring and monitoring raw materials, cell culture, purification, and cleaning and lyophilization processes via advanced PAT. They also explore how data are collected and analyzed using advanced analytical techniques such as multivariate data analysis, monitoring, and control in real-time. Invaluable for experienced practitioners in PAT in biopharmaceuticals, this book is an excellent reference guide for regulatory officials and a vital training aid for students who need to learn the state of the art in this interdisciplinary and exciting area.

Monoclonal antibodies have become important treatments for cancer, inflammation and a wide range of other diseases, representing an increasing share of the most successful pharmaceutical markets. The technologies to discover these drugs have been developed by select centers of excellence in industry and academia, and are continually being fine tuned in the race to identify the best antibody-based drug candidates and accelerate their paths to patients. The objective of this volume is to provide a series of guides to those evaluating and preparing to enter particular areas within the field and to offer specialized perspectives to established researchers. The chapters set into context the significance of key developments and important considerations for selecting different approaches, such as antibody humanization, isotype selection, lead candidate selection criteria and protein production. All contributors to this work are experts in their fields, and many have played pivotal roles in the creation of these technologies.

The modern synthetic chemist applies all the tools available to identify the drug-like molecules with the best chances of becoming novel drugs. This book will act as a primer for graduates and postgraduates interested in a career in drug discovery. It covers both synthetic technologies currently impacting medicinal chemistry and emerging areas. The chapters focus on topics including: parallel medicinal chemistry; solid supported reagents; microwave assisted chemistry; flow synthesis, and high throughput reaction screening.

Bioactive natural products are a rich source of novel therapeutics. Thus, the search for bioactive molecules from nature continues to play an important role in fashioning new medicinal agents. This volume, which comprises sixteen chapters written by active researchers and leading experts in natural products chemistry, brings together an overview of current discoveries in this remarkable field. It also provides information on the industrial application of natural products for medicinal purposes. This book will serve as a valuable resource for researchers to predict promising leads for developing pharmaceuticals to treat various ailments and disease manifestations.

The approach to drug discovery from natural sources has yielded many important new pharmaceuticals inaccessible by other routes. In many cases the isolated natural product may not be an effective drug for any of several reasons, but it nevertheless may become a drug through chemical modification or have a novel pharmacophore for future drug design. In summarizing the status of natural products as cancer chemotherapeutics, Anticancer Agents from Natural Products, Second Edition covers the: History of each covered drug-a discussion of its mechanism on action, medicinal chemistry, synthesis, and clinical applications Potential for novel drug discovery through the use of genome mining as well as future developments in anticancer drug discovery Important biosynthetic approaches to "unnatural" natural products Anticancer Agents from Natural Products, Second Edition discusses how complex target-oriented synthesis-enabled by historic advances in methodology-has enormously expanded the scope of the possible. This book covers the current clinically used anticancer agents that are either natural products or are clearly derived from natural product leads. It also reviews drug candidates currently in clinical development since many of these will be clinically used drugs in the future. Examples include the drugs etoposide and teniposide derived from the lead compound podophyllotoxin; numerous analogs derived from taxol; topotecan, derived from camptothecin; and the synthetic clinical candidates, E7389 and HTI-286, developed from the marine leads, halichondrin B and hemiasterlin.

The deregulation of dietary supplements and natural products marketing by the FDA has widened the natural products market in Europe and worldwide. While the discussion about the validity of the plant approach to nutrition and diseases treatment continues, the explosion of the use of whatever is considered "natural" has generated concern about effectiveness and danger. Incorporating information ranging from regulatory aspects to clinical trial and vigilance, Herbal Medicines: Development and Validation of Plant-Derived Medicines for Human Health: Provides a reference model for those who would like to start the R&D process for a natural product Discusses fundamental issues in the development of traditional medicines for the benefit of human health Takes a sequential rational approach to the subject matter Brings awareness to the many problems facing the development of medicinal herbal products, such as quality control, pharmacokinetic, and pharmacodynamic issues This book takes readers on a rational path for development of efficacious medicinal herbal products. It points out the many problems facing the development of these products, such as quality control, pharmacokinetic, and pharmacodynamic issues. It suggests areas where future developments should occur given healthcare needs and public health considerations.

The book provides valuable information on wild plants and their ethnopharmacological properties, discussion on ethnobotany, phytotherapy, diversity, chemical and pharmacological properties including antifungal, anti-inflammatory and antiprotozal properties. The chapters include a wide range of case studies, giving updated evidence on importance of wild plant resources from different countries including Nepal, India, Brazil, Chile, Argentina, Colombia, Egypt, Peru, etc. In addition, some specific species are used to explain their potential properties. Discussing traditional usage and pharmacological properties of wild plants, this book is entirely different from other related publications and useful for the researchers working in the areas of conservation biology, botany, ethnobiology, ethnopharmacology, policy making, etc.

The first edition of Pharmaceutical Extrusion Technology, published in 2003, was deemed the seminal book on pharmaceutical extrusion. Now it is expanded and improved, just like the usage of extrusion has expanded, improved and evolved into an accepted manufacturing technology to continuously mix active pharmaceutical ingredients with excipients for a myriad of traditional and novel dosage forms. Pharmaceutical Extrusion Technology, Second Edition reflects how this has spawned numerous research activities, in addition to hardware and process advancements. It offers new authors, expanded chapters and contains all the extrusion related technical information necessary for the development, manufacturing, and marketing of pharmaceutical dosage forms. Key Features: Reviews how extrusion has become an accepted technology to continuously mix active pharmaceutical ingredients with excipients Focuses on equipment and process technology Explains various extrusion system configurations as a manufacturing methodology for a variety of dosage forms Presents new opportunities available only via extrusion and future trends Includes contributions of experts from the process and equipment fields

In a global clinical development strategy, multiregional clinical trials (MRCTs) are vital in the development of innovative medicines. Multiregional Clinical Trials for Simultaneous Global New Drug Development presents a comprehensive overview on the current status of conducting MRCTs in clinical development. International experts from academia, industry, and health organizations address various aspects of the important problems in global clinical development and MRCTs. The book first provides a high-level introduction to the context, motivation, opportunities, and challenges in simultaneous global clinical development using MRCTs. It then focuses on the design, monitoring, and analysis/interpretation of MRCTs. The book concludes with an examination of the latest research topics from MRCT perspectives, such as special considerations by local health authorities, health economic evaluations, benefit-risk assessment, and medical devices. Explaining how to design, conduct, and interpret MRCTs, this book will help biostatisticians working in the late-stage clinical development of medical products. It will also be useful for statisticians and clinicians in the biopharmaceutical industry, regulatory agencies, and medical research institutes.

Develop Effective Immunogenicity Risk Mitigation Strategies Immunogenicity assessment is a prerequisite for the successful development of biopharmaceuticals, including safety and efficacy evaluation. Using advanced statistical methods in the study design and analysis stages is therefore essential to immunogenicity risk assessment and mitigation strategies. Statistical Methods for Immunogenicity Assessment provides a single source of information on statistical concepts, principles, methods, and strategies for detection, quantification, assessment, and control of immunogenicity. The book first gives an overview of the impact of immunogenicity on biopharmaceutical development, regulatory requirements, and statistical methods and strategies used for immunogenicity detection, quantification, and risk assessment and mitigation. It then covers anti-drug antibody (ADA) assay development, optimization, validation, and transfer as well as the analysis of cut point, a key assay performance parameter in ADA assay development and validation. The authors illustrate how to apply statistical modeling approaches to establish associations between ADA and clinical outcomes, predict immunogenicity risk, and develop risk mitigation strategies. They also present various strategies for immunogenicity risk control. The book concludes with an explanation of the computer codes and algorithms of the statistical methods. A critical issue in the development of biologics, immunogenicity can cause early termination or limited use of the products if not managed well. This book shows how to use robust statistical methods for detecting, quantifying, assessing, and mitigating immunogenicity risk. It is an invaluable resource for anyone involved in immunogenicity risk assessment and control in both non-clinical and clinical biopharmaceutical development.

Discover the Latest Statistical Approaches for Modeling Exposure-Response Relationships Written by an applied statistician with extensive practical experience in drug development, Exposure-Response Modeling: Methods and Practical Implementation explores a wide range of topics in exposure-response modeling, from traditional pharmacokinetic-pharmacodynamic (PKPD) modeling to other areas in drug development and beyond. It incorporates numerous examples and software programs for implementing novel methods. The book describes using measurement error models to treat sequential modeling, fitting models with exposure and response driven by complex dynamics, and survival analysis with dynamic exposure history. It also covers Bayesian analysis and model-based Bayesian decision analysis, causal inference to eliminate confounding biases, and exposure-response modeling with response-dependent dose/treatment adjustments (dynamic treatment regimes) for personalized medicine and treatment adaptation. Many examples illustrate the use of exposure-response modeling in experimental toxicology, clinical pharmacology, epidemiology, and drug safety. Some examples demonstrate how to solve practical problems while others help with understanding concepts and evaluating the performance of new methods. The provided SAS and R codes enable readers to test the approaches in their own scenarios. Although application oriented, this book also gives a systematic treatment of concepts and methodology. Applied statisticians and modelers can find details on how to implement new approaches. Researchers can find topics for or applications of their work. In addition, students can see how complicated methodology and models are applied to practical situations.

Design and Analysis of Clinical Trials for Predictive Medicine provides statistical guidance on conducting clinical trials for predictive medicine. It covers statistical topics relevant to the main clinical research phases for developing molecular diagnostics and therapeutics-from identifying molecular biomarkers using DNA microarrays to confirming their clinical utility in randomized clinical trials. The foundation of modern clinical trials was laid many years before modern developments in biotechnology and genomics. Drug development in many diseases is now shifting to molecularly targeted treatment. Confronted with such a major break in the evolution toward personalized or predictive medicine, the methodologies for design and analysis of clinical trials is now evolving. This book is one of the first attempts to contribute to this evolution by laying a foundation for the use of appropriate statistical designs and methods in future clinical trials for predictive medicine. It is a useful resource for clinical biostatisticians, researchers focusing on predictive medicine, clinical investigators, translational scientists, and graduate biostatistics students.

The growing interest in using combination drugs to treat various complex diseases has spawned the development of many novel statistical methodologies. The theoretical development, coupled with advances in statistical computing, makes it possible to apply these emerging statistical methods in in vitro and in vivo drug combination assessments. However, despite these advances, no book has served as a single source of information for statistical methods in drug combination research, nor has there been any guidance for experimental strategies. Statistical Methods in Drug Combination Studies fills that gap, covering all aspects of drug combination research, from designing in vitro drug combination studies to analyzing clinical trial data. Featuring contributions from researchers in industry, academia, and regulatory agencies, this comprehensive reference: Describes statistical models used to characterize dose-response patterns of monotherapies and evaluate the combination drug synergy Offers guidance for estimating interaction indices and constructing their associated confidence intervals to assess drug interaction Introduces a practical and innovative Bayesian approach to Phase I cancer trials, including actual trial examples to illustrate use Examines strategies in the fixed-dose combination therapy clinical development via case studies stemming from regulatory reviews Evaluates computational tools and software packages used to apply novel statistical methods in combination drug development Statistical Methods in Drug Combination Studies provides researchers with a solid understanding of the available statistical methods and computational tools and how to apply them in drug combination studies. The book is equally useful for statisticians to become better equipped to deal with drug combination study design and analysis in their practice.

In order to understand drug metabolism at its most fundamental level, pharmaceutical scientists must be able to analyze drug compound structure and predict possible metabolic pathways in order to avoid the risk of adverse reactions that lead to the withdrawal of a drug from the market. This title is a comprehensive guide for recognizing the chemical underpinnings of drug metabolism. While there are numerous resources available to medicinal chemists for understanding drug structure, and to pharmacologists for discerning drug metabolism from a biological standpoint, no resource currently exists that links the chemical and biological aspects in language accessible to both-making it challenging for both groups to fully comprehend how a drug is metabolized, as well as the potential effects of the metabolites. Drug Metabolism: Chemical and Enzymatic Aspects provides extensive material to help understand drug metabolism within a biological context, and for predicting and mitigating adverse drug reactions.

Carefully crafted to provide tightly focused and authoritative information, the Directory of Therapeutic Enzymes covers all approved therapeutic enzymes currently used in medicine. Written mainly by industry experts, the book includes information sourced directly from the company that developed or manufactured the product. It explores major development issues, from manufacturing and marketing to delivery of the finished product. Chapter 1 reviews applied enzymology while chapter 2 delineates theory and applications. Between them, the first two chapters set the appropriate backdrop for the remaining chapters, which focus on actual enzyme products that have gained regulatory approval for general medical use. The chapter authors discuss the biochemistry of the enzymes, the reactions they catalyze, how they are produced or manufactured, and their medical applications. The book highlights the many applications of approved therapeutic enzymes, including use in the treatment of blood-clotting disorders, certain cancers, and a variety of genetic disorders. Illustrated with tables and figures that support the text, the book is a single source of in-depth technical information.

The concept of frailty offers a convenient way to introduce unobserved heterogeneity and associations into models for survival data. In its simplest form, frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or a group of related individuals. Frailty Models in Survival Analysis presents a comprehensive overview of the fundamental approaches in the area of frailty models. The book extensively explores how univariate frailty models can represent unobserved heterogeneity. It also emphasizes correlated frailty models as extensions of univariate and shared frailty models. The author analyzes similarities and differences between frailty and copula models; discusses problems related to frailty models, such as tests for homogeneity; and describes parametric and semiparametric models using both frequentist and Bayesian approaches. He also shows how to apply the models to real data using the statistical packages of R, SAS, and Stata. The appendix provides the technical mathematical results used throughout. Written in nontechnical terms accessible to nonspecialists, this book explains the basic ideas in frailty modeling and statistical techniques, with a focus on real-world data application and interpretation of the results. By applying several models to the same data, it allows for the comparison of their advantages and limitations under varying model assumptions. The book also employs simulations to analyze the finite sample size performance of the models.