A comprehensive review of the challenges that exist in patient accessibility to advanced therapy medicinal products (ATMPs), presenting clinical trials, marketing authorization, HTA, pricing, reimbursement, affordability, payment and partnership agreements of RMs and commercialisation. Specfically, we investigated how COVID-19 has impacted the RMs industry by elaborating on the disruptions it caused but also the new opportunities it brought. The ultimate goal of this work is to make strategic recommendations for manufacturers and decisions-markers on effective strategies to address the above obstacles and facilitate patient access to promising regenerative medicines. Features : Regenerative medicine (RM) is an emerging interdisciplinary field aiming to replace or regenerate human cells, tissues, or organs in order to restore normal functions. Regenerative medicine holds the promise of revolutionising treatment in the 21st century. RMs bring new hope for some previously untreatable diseases, as well as holding promise for the treatment of common chronic diseases. Rapid advancements in biotechnology and improved understanding of disease pathophysiology have attracted tremendous interests in the development of RMs. Discusses the high cost of RMs which may challenge the sustainability of healthcare insurers (public and private).

This detailed volume presents a series of protocols dealing with different aspects of inclusion body (IB) processing, from cloning procedures to purification of refolded product. Commencing with chapters on upstream processing, looking into different expression strategies for IB production, the book continues with downstream applications, highlighting early protein purification and subsequent analytics, as well as success stories of IB-based processes. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Inclusion Bodies: Methods and Protocols serves as an ideal resource for facilitating diverse aspects of IB processing.

Aging is an inevitable part of life and is becoming a worldwide social, economic and health problem. This is mainly due to the fact that the increasing proportion of individuals in the advanced age category have a higher probability of developing age-related disorders, such as type II diabetes mellitus, cardiovascular disorders, sarcopenia, and neurodegenerative conditions. New therapeutic approaches are still needed to decrease or slow the effects of such diseases. Advances in -omic technologies, such as genomics, transcriptomics, proteomics and metabolomics, have significantly advanced our understanding of disease in multiple medical areas, as the analysis of multiple molecular networks has simultaneously provided a more integrated view of disease pathways. It is hoped that emerging hits from these analyses might be prioritized for further screening as potential novel drug targets for increasing the human healthspan in line with the lifespan. In turn, this will lead to new therapeutic strategies as well as drug development projects by the pharmaceutical industry. This book presents a series of reviews describing studies that have resulted in identification of new potential drug targets for age-related disorders. Much of this information has come from -omic comparisons of healthy and disease states or from testing the effects of new therapeutic approaches. Authored by experts from around the globe, each chapter is presented in the context of specific chronic diseases or therapeutic strategies. This book is designed for researchers in the areas of aging and chronic disease, as well as clinical scientists, physicians and stakeholders in major drug companies.

This book begins with an introduction of pragmatic cluster randomized trials (PCTs) and reviews various pragmatic issues that need to be addressed by statisticians at the design stage. It discusses the advantages and disadvantages of each type of PCT, and provides sample size formulas, sensitivity analyses, and examples for sample size calculation. The generalized estimating equation (GEE) method will be employed to derive sample size formulas for various types of outcomes from the exponential family, including continuous, binary, and count variables. Experimental designs that have been frequently employed in PCTs will be discussed, including cluster randomized designs, matched-pair cluster randomized design, stratified cluster randomized design, stepped-wedge cluster randomized design, longitudinal cluster randomized design, and crossover cluster randomized design. It demonstrates that the GEE approach is flexible to accommodate pragmatic issues such as hierarchical correlation structures, different missing data patterns, randomly varying cluster sizes, etc. It has been reported that the GEE approach leads to under-estimated variance with limited numbers of clusters. The remedy for this limitation is investigated for the design of PCTs. This book can assist practitioners in the design of PCTs by providing a description of the advantages and disadvantages of various PCTs and sample size formulas that address various pragmatic issues, facilitating the proper implementation of PCTs to improve health care. It can also serve as a textbook for biostatistics students at the graduate level to enhance their knowledge or skill in clinical trial design. Key Features: Discuss the advantages and disadvantages of each type of PCTs, and provide sample size formulas, sensitivity analyses, and examples. Address an unmet need for guidance books on sample size calculations for PCTs; A wide variety of experimental designs adopted by PCTs are covered; The sample size solutions can be readily implemented due to the accommodation of common pragmatic issues encountered in real-world practice; Useful to both academic and industrial biostatisticians involved in clinical trial design; Can be used as a textbook for graduate students majoring in statistics and biostatistics.

The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors, and researchers. Ion channels are membrane proteins that control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli like light, sound, odor, and taste, and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical applications. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume II starts with ion channel taxonomy and features coverage of major ion channel families and describes the physiological role, structural components, gating mechanisms and biophysics, permeation and selectivity, regulation, pharmacology and roles in disease mechanisms. Channels in this volume include voltage-activated sodium, calcium and potassium channels, inward-rectifier and two-pore domain potassium channels, calcium-activated potassium channels, cyclic-nucleotide gated channels, pacemaker ion channels, chloride channels, the ligand-gated receptors activated by acetylcholine, glutamate, 5-HT3, GABA and glycine, acid-sensing channels, P2X receptors, TRP channels, store-operated channels, pressure-activated piezo channels, ryanodine receptors and proton channels. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels, a guide to the technical aspects of ion channel research, offer a modern guide to the properties of major ion channel families, and include coverage of key examples of regulatory, physiological, and disease roles for ion channels.

The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors, and researchers. Ion channels are membrane proteins that control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli like light, sound, odor, and taste, and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical applications. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume III includes coverage of key ion channel regulators and their mechanisms, the role of ion channels working in concert in selected physiological systems, and examples of ion channel mutations and dysfunction in a selection of diseases. Chapters on ion channel regulation include splice variants, calcium-calmodulin regulation, regulation by G-proteins, and lipids. A selection of ion channels in physiological systems includes ion channels of the heart, ion channels in immune cells and their role in pancreatic beta cells and regulation of insulin secretion, and the role of channels in sperm and eggs. While disease mechanisms are integrated into the chapters of Volume II, Volume III offers special consideration of ion channels in epilepsy, cystic fibrosis, and pain syndromes. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels, a guide to the technical aspects of ion channel research, offer a modern guide to the properties of major ion channel families, and include coverage of key examples of regulatory, physiological, and disease roles for ion channels.

Worldwide interest in Ayurveda is on the rise, ever since the World Health Organization adopted the Alma Ata Declaration in 1978. Ayurveda is increasingly being adopted and many phytotherapy schools in Europe and the Americas teach Ayurveda as a wellness system. Considering the prominent position that Aṣṭ�ṅgahṛdaya occupies in Ayurveda, a scientific synopsis of this masterpiece is now presented before the world of Ayurveda. In eight comprehensive chapters, Aṣṭ�ṅgahṛdaya: A Scientific Synopsis of the Classic Ayurveda Text presents a lucid summary of the teachings of V�gbhaṭa. Ayurvedic view of the human body, basic principles of Ayurveda, surgical armamentarium, diagnosis and treatment of diseases, herbs and other medicinal substances used in the preparation of various dosage forms, ayurvedic pharmaceutialcs, ayurvedic approach to food fortification, salient features of Aṣṭ�ṅgahṛdaya and a roadmap for the future are among the topics discussed. Key Features: Presents the ayurvedic view of conception and the human body. Discusses aspects of ayurvedic pharmaceuticals. Examines diagnosis of diseases, lines of treatment, prognosis of diseases, signs of imminent death, management of mishaps and treatment of new diseases. The voluminous information pertaining to the subjects of the various chapters is presented in the form of many tables for ready reference and quick survey. This book provides a helping hand to those interested in rediscovering the teachings of V�gbhaṭa and is a great resource for researchers of medicine, traditional and alternative medicine, pharmacology and drug discovery.

An outstanding resource which enables readers to better understand the conditions that led to these Nobel Prize amazing discoveries To an extent the roots of organic chemistry have been forgotten or lost and this set of volumes bridges the gap Unique set of volumes, no other book publication in the field competes and only press releases announcing the prizes from recent years exist "More than any other branch of chemistry, organic chemists look to history, so the readers will certainly enjoy this compilation " Appeals to a diverse audience including upcoming as well as modern practicing chemists, and provides the historical context of these discoveries

This book provides a comprehensive overview of the biosimilar regulatory framework, the development process and clinical aspects for development of biosimilars. The development path of a biosimilar is just as unique as a development path of a new drug, tailored by the mechanism of action, the quality of the molecule, published information on the reference product, the current competitive environment, the target market and regulatory guidance, and most importantly, the emerging totality of evidence for the proposed biosimilar during development. For the ease of readers, the book comprises of six sections as follows: Section I: Business, Health Economics and Intellectual Property Landscape for Biosimilars Section II: Regulatory Aspects of Development and Approval for Biosimilars Section III: Biopharmaceutical Development and Manufacturing of Biosimilars Section IV: Analytical Similarity Considerations for Biosimilars Section V: Clinical aspects of Biosimilar Development Section VI: Biosimilars- Global Development and Clinical Experience Chapters have been written by one or more experts from academia, industry or regulatory agencies who have been involved with one or more aspects of biosimilar product development. The authors and editors have an expertise in commercialization and pricing of biosimilars, intellectual property considerations for biosimilars, chemistry manufacturing controls (CMC) and analytical development for biosimilars, regulatory and clinical aspects of biosimilar development. Besides the industry practitioners, the book includes several contributions from regulators across the globe.

This book offers a fresh look on a variety of issues concerning herbal medicine - the methods of growing and harvesting various medicinal plants; their phytochemical content; medicinal usage; regulatory issues; and mechanism of action against myriad of human and animal ailments. 'Medicinal Plants: From Farm to Pharmacy' comprises chapters authored by renowned experts from academics and industry from all over the world. It provides timely, in-depth study/analysis of medicinal plants that are already available in the market as supplements or drug components, while also introducing several traditional herbs with potential medicinal applications from various regions of the world. The book caters to the needs of a diverse group of readers: plant growers, who are looking for ways to enhance the value of their crops by increasing phytochemical content of plant products; biomedical scientists who are studying newer applications for crude herbal extracts or isolated phytochemicals; clinicians and pharmacologists who are studying interactions of herbal compounds with conventional treatment modalities; entrepreneurs who are navigating ways to bring novel herbal supplements to the market; and finally, natural medicine enthusiasts and end-users who want to learn how herbal compounds are produced in nature, how do they work and how are they used in traditional or modern medicine for various disease indications.

Worldwide interest in Ayurveda is on the rise, ever since the World Health Organization adopted the Alma Ata Declaration in 1978. Ayurveda is increasingly being adopted and many phytotherapy schools in Europe and the Americas teach Ayurveda as a wellness system. Considering the prominent position that Aṣṭ�ṅgahṛdaya occupies in Ayurveda, a scientific synopsis of this masterpiece is now presented before the world of Ayurveda. In eight comprehensive chapters, Aṣṭ�ṅgahṛdaya: A Scientific Synopsis of the Classic Ayurveda Text presents a lucid summary of the teachings of V�gbhaṭa. Ayurvedic view of the human body, basic principles of Ayurveda, surgical armamentarium, diagnosis and treatment of diseases, herbs and other medicinal substances used in the preparation of various dosage forms, ayurvedic pharmaceutialcs, ayurvedic approach to food fortification, salient features of Aṣṭ�ṅgahṛdaya and a roadmap for the future are among the topics discussed. Key Features: Presents the ayurvedic view of conception and the human body. Discusses aspects of ayurvedic pharmaceuticals. Examines diagnosis of diseases, lines of treatment, prognosis of diseases, signs of imminent death, management of mishaps and treatment of new diseases. The voluminous information pertaining to the subjects of the various chapters is presented in the form of many tables for ready reference and quick survey. This book provides a helping hand to those interested in rediscovering the teachings of V�gbhaṭa and is a great resource for researchers of medicine, traditional and alternative medicine, pharmacology and drug discovery.

This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.

Thanks to their unique properties, chitosan and chitosan-based materials have numerous applications in the field of biomedicine, especially in drug delivery. This book examines biomedical applications of functional chitosan, exploring the various functions and applications in the development of chitosan-based biomaterials. It also describes the chemical structure of chitosan and discusses the relationship between their structure and functions, providing a theoretical basis for the design of biomaterials. Lastly, it reviews chemically modified and composite materials of chitin and chitosan derivatives for biomedical applications, such as tissue engineering, nanomedicine, drug delivery, and gene delivery.

This comprehensive volume provides an update on the current state of pharmacometrics in drug development. It consists of nineteen chapters all written by leading scientists from the pharmaceutical industry, regulatory agencies and academia. After an introduction of the basic pharmacokinetic and pharmacodynamic concepts of pharmacometrics in drug development, the book presents numerous examples of specific applications that utilize pharmacometrics with modeling and simulations over a variety of therapeutic areas, including pediatrics, diabetes, obesity, infections, psychiatrics, Alzheimer's disease, and dermatology, among others. The examples illustrate how results from all phases of drug development can be integrated in a more timely and cost-effective process. Applying pharmacometric decision tools during drug development can allow objective, data-based decision making. At the same time, the process can identify redundant or unnecessary experiments as well as some costly clinical trials that can be avoided. In addition to cost saving by expedited development of successful drug candidates, pharmacometrics has an important economic impact in drug product selection. Unsuccessful drug candidates can be identified early and discontinued without expending efforts required for additional studies and allocating limited resources. Hence, pharmacometric modeling and simulation has become a powerful tool to bring new and better medications to the patient at a faster pace and with greater probability of success.

The applications of nanoparticulate drug delivery have gained significant attention in cancer diagnosis and treatment. Owing to their unique features and design, nanomedicines have made remarkable progress in eliminating dreadful tumors. Research in cancer nanomedicine spans multitudes of drug-delivery systems that include high tumor-targeting ability, sensitivity toward tumor microenvironments, and improved efficacy. Various nanocarriers have been developed and approved for anti-tumor drug targeting. These nanocarriers, such as liposomes, micelles, nanotubes, dendrimers, and peptides, offer several advantages including high selectivity, multifunctionality, specificity, biocompatibility, and precise control of drug release. This book provides complete information about each aspect of nanomaterials and nanotherapeutics, including synthesis, analysis, disease diagnosis, mechanistic insight, targeted drug delivery, and clinical implications in a concise and informative way. It presents simple and reader-friendly representations of the mechanisms of action of nanomaterials on cellular targets and highlights the challenges in targeted drug delivery with ongoing chemotherapeutic drugs.

This handbook provides an in-depth review of information across the developmental spectrum of gene and cell therapy products. From introductory information to state-of-the-art technologies and concepts, the book provides insights into upstream processes such as vector design and construction, purification, formulation and fill/finish as well as delivery options. Planning steps for compliance with current good manufacturing practice (CGMP) to readiness for chemistry, manufacturing, and controls (CMC) are also discussed.This book wraps up with examples of successes and pitfalls addressed by experts who have navigated the multiple challenges that are part of any innovative endeavor. Features Intended as a one-stop resource for availability of state-of-the-art information related to cell and gene therapy products for researchers, scientists, management and other academic and research institutions. Provides the most up to date information on the development of gene therapy, from the technology involved to gene correction and genome editing. Discusses siRNA, mRNA, and plasmid manufacturing. Describes the importance of supplier-sponsor synergies on the path to commercialization. Diverse audience with a large number of individuals in the core technologies and supportive practices.

This book explains theoretical and technological aspects of amorphous drug formulations. It is intended for all those wishing to increase their knowledge in the field of amorphous pharmaceuticals. Conversion of crystalline material into the amorphous state, as described in this book, is a way to overcome limited water solubility of drug formulations, in this way enhancing the chemical activity and bioavailability inside the body. Written by experts from various fields and backgrounds, the book introduces to fundamental physical aspects (explaining differences between the ordered and the disordered solid states, the enhancement of solubility resulting from drugs amorphization, physical instability and how it can be overcome) as well as preparation and formulation procedures to produce and stabilize amorphous pharmaceuticals. Readers will thus gain a well-funded understanding and find a multi-faceted discussion of the properties and advantages of amorphous drugs and of the challenges in producing and stabilizing them. The book is an ideal source of information for researchers and students as well as professionals engaged in research and development of amorphous pharmaceutical products.

This book covers a wide range of topics concerning human tear based science, starting from basics such as the normal composition of tears and moving up to novel disease detection platforms. The entire approach is pioneering, as tears are beginning to be recognized as the most invaluable non-invasive tool in diagnostics. Interestingly, the concept is not restricted to ocular diseases: In recent years, tear diagnostics is increasingly being tapped even for cancer detection. Hopefully, non-invasive tear diagnostics will eventually replace today's invasive disease detection and monitoring techniques. Previous literature on tear diagnostics has been restricted to scientific journal articles, most of which dealt with a single tear constituent, such as a protein. This book offers a far more comprehensive and handy 'reference guide,' presenting both basic and advanced information and data. Accordingly, it will be useful for researchers in academia and the pharmaceutical industry, as well as healthcare professionals and diagnostic kit developers.

Plant-based medicines and aromatics are increasingly in demand throughout the health sector globally, which involves their use not only for the treatment of diseases, but also as potential therapeutics standards for maintaining good health. Unlike modern medicine, herbal medicines derived from plants have several major advantages, including general absence of serious adverse side effects, long-lasting curative impact, and overall cost-effectiveness. Medicinal plants have become threatened due to their minuscule population size, narrow distribution area, habitat specificity, and destructive way of harvesting, only a few studies have been undertaken on their conservation, ecology and pharmacognosy.

Key Features: 1. Describes the development of the randomized, controlled trial as the gold standard of proof. 2. Unravels the meaning of "randomized," "double-blind" and "p-values" in a simplified manner for students and clinicians. 3. Contains timeless information on how medical evidence can be understood.

Real-world evidence (RWE) has been at the forefront of pharmaceutical innovations. It plays an important role in transforming drug development from a process aimed at meeting regulatory expectations to an operating model that leverages data from disparate sources to aid business, regulatory, and healthcare decision making. Despite its many benefits, there is no single book systematically covering the latest development in the field. Written specifically for pharmaceutical practitioners, Real-World Evidence in Drug Development and Evaluation, presents a wide range of RWE applications throughout the lifecycle of drug product development. With contributions from experienced researchers in the pharmaceutical industry, the book discusses at length RWE opportunities, challenges, and solutions. Features Provides the first book and a single source of information on RWE in drug development Covers a broad array of topics on outcomes- and value-based RWE assessments Demonstrates proper Bayesian application and causal inference for real-world data (RWD) Presents real-world use cases to illustrate the use of advanced analytics and statistical methods to generate insights Offers a balanced discussion of practical RWE issues at hand and technical solutions suitable for practitioners with limited data science expertise

This book, which is the third volume of Biomedical translational research, focuses on the fundamental role of biomedical research in developing new medicinal products. It emphasizes the importance of understanding biological and pathophysiological mechanisms underlying the disease to discover and develop new biological agents. The book uniquely explores the genomic computational integrative approach for drug repositioning. Further, it discusses the health benefits of nutraceuticals and their application in human diseases. Further, the book comprehensively reviews different computational approaches that employ GWAS data to guide drug repositioning. Finally, it summarizes the major challenges in drug development and the strategies for the rational design of the next generation more effective but less toxic therapeutic agents.

This book covers various aspects of cancer chemoprevention, including an overview of chemoprevention in the process of tumorigenesis; the roles of various phytochemicals, functional foods, and dietary interventions in disease prevention; and techniques such as cancer stem cell targeting, nano-formulations, and so forth. The nutrigenomic and epigenetic effects of natural products at the molecular and genetic levels are also covered alongside their potential for additive and synergistic effect, as well as overcoming drug resistance. The key selling features of the book are as follows: Discusses holistic and comprehensive areas of chemoprevention Includes diverse techniques, such as cancer stem cell targeting, nano-formulations, and nanotechnology-based drug delivery systems Introduces various mechanisms involved in prevention of the diseases, including targeting cancer stem cells Reviews various aspects which can reduce the toxicity and cost of treatment of diseases by alternative medicine Explores various sources, mechanisms, and ways to develop cancer chemopreventive agents with minimal toxicity compared to traditional cancer therapy drugs This book is focused on researchers and graduate students in drug delivery and formulation, nanobiotechnology, cancer chemoprevention, prevention, and therapeutics.

This book deals with the recent advances in DNA-Encoded Library (DEL) technology that has emerged as an alternative to high throughput screening (HTS) over the last decade and has been heralded as a "disruptive" technology for drug discovery. The book aims to provide a comprehensive overview of all of the major components of the DEL process from conception to bench execution and clinical investigations. The contributions from experts in the field combine different perspectives from academia and industry. The book will be of interest to researchers in the drug discovery field as well as to graduate students and scholars who are interested in this rapidly improving technology.

General compendium of HDAC inhibitors with deep emphasis on toxicity issues of synthetic HDAC inhibitors Various groups of natural HDAC inhibitors, their representatives and premier sources Cyclic tetrapeptides of natural origin and their importance as cancer chemotherapeutic agents Hydroxamates and depsipeptides from natural sources and their promising role in cancer therapy Natural Flavonoids, their HDAC inhibitory tendency and marvellous anticancer activity Non-flavonoid natural HDAC inhibitors and their pleasing cytotoxic effects towards cancer models Combined therapy involving natural flavonoids with other anticancer molecules for synergistic and additive benefits against cancer models Non-flavonoid HDAC inhibitors and conventional drugs in collaborative mode against aggressive malignancies Nanotechnology based delivery of natural HDAC inhibitors for greater therapeutic efficacy over traditional combinatorial therapy