Provides a review of novel pharmaceutical approaches for Tuberculosis drugs Presents a novel perspective on tuberculosis prevention and treatment Considers the nature of disease, immunological responses, vaccine and drug delivery, disposition and response Multidisciplinary appeal, with contributions from microbiology, immunology, molecular biology, pharmaceutics, pharmacokinetics, chemical and mechanical engineering INDICE: Contributors .Foreword .Advances in Pharmaceutical Technology: Series Preface .Preface .1 Introduction: A guide to treatment and prevention of tuberculosis based on principles of dosage form design and delivery .1.1 Background .1.2 Dosage Form Classification .1.3 Dosage Forms .1.4 Controlled and Targeted Delivery .1.5 Physiological and Disease Consideration .1.6 Therapeutic Considerations .1.7 Conclusion .References .2 Host Pathogen Biology for Airborne Mycobacterium tuberculosis: Cellular and Molecular Events in the Lung .2.1 Introduction .2.2 Lung .2.3 General Aspects of Mucus and Surfactant .2.4 General M. tuberculosis .2.5 M. tuberculosis Interaction with the Lung Macrophage .2.6 M. tuberculosis Interaction with other Respiratory Immune Cells .2.7 TB Granuloma .2.8 Conclusion .References .3 Animal Models of Tuberculosis .3.1 Introduction .3.2 What is an animal model of TB? .3.3 How are animal models of TB used? .3.4 TB animal models currently used for TB drug and vaccine evaluation .3.5 Summary .References .4 Vaccine Preparation: Past, Present and Future .4.1 Introduction .4.2 Early efforts in TB vaccine development .4.2.1 Early BCG formulation and manufacturing .4.2.2 History of the BCG vaccine and routes .4.2.3 Quality control issues .4.3 Current BCG vaccine formulation .4.3.1 BCG vaccine strain variability .4.3.2 Manufacturing Process .4.3.3 Packing and Storage .4.3.4 Transportation .4.3.5 Needle–stick issues .4.4 Novel TB vaccination strategies .4.4.1 Formulation and stabilization techniques .4.4.1.1 Vaccine formulation .4.4.1.2 Adjuvants .4.4.1.3 Excipient selection .4.4.2 Manufacturing of TB vaccines .4.4.2.1 Whole cell vaccine .4.4.2.2 Subunit vaccines .4.4.3 Regulatory approval process .4.4.4 Vaccine Packaging .4.5 Future perspective .4.6 Conclusion .References .5 TB Vaccine Assessment .5.1 Introduction .5.2 Pre–clinical Vaccine Assessment .5.2.1 Murine Model .5.2.2 Guinea Pig Model .5.2.3 Cattle Model .5.2.4 Non–human Primate Model .5.3 Clinical assessment of vaccines .5.3.1 Human Clinical Trials And Phases Of Testing .5.3.2 Live Attenuated Vaccine Candidates .5.3.3 Viral Vectored Subunit Vaccines .5.3.4 Adjuvanted Subunit Vaccines .5.3.5 Therapeutic Vaccines .5.3.6 Route of Immunization .5.4 Laboratory Immunological Analysis and Assessment of Vaccine Trials .5.4.1 Decision on Population of Interest .5.4.2 Detection of Infection .5.4.3 Detection of Protective Immunity .5.5 How well do the available preclinical models predict vaccine success in humans? .References .6 Testing Inhaled Drug Therapies for Treating Tuberculosis .6.1 Introduction .6.2 The Need for New Drug Treatments for Tuberculosis .6.3 Inhaled Drug Therapy for Tuberculosis .6.4 Published Studies of Inhalation Therapy for TB .6.5 The Guinea Pig Model for Testing Inhaled Therapies for TB .6.6 Guinea Pig Study Design .6.7 Purchase and Grouping Animals .6.8 Infecting Guinea Pigs with Virulent Mycobacterium tuberculosis .6.9 Dosing Groups of Guinea Pigs with TB Drugs .6.10 Collecting Data .6.11 Aerosol Dosing Chambers and Practice .6.12 Nebulizer Aerosol Delivery Systems for Liquids .6.13 Dry Powder Aerosol Delivery Systems for Solids .6.14 Summary .Acknowledgments .References .7 Preclinical Pharmacokinetics of Antitubercular Drugs .7.1 Introduction .7.2 Factors Influencing the Pharmacokinetic Behavior of Drugs .7.2.1 Physicochemical properties of the drug .7.2.2 Formulation and routes of administration .7.2.3 Disease state .7.3 Pulmonary Delivery of anti–TB Drugs .7.4 Pharmacokinetic Study Design .7.4.1 Animal Models .7.4.2 Biological Samples .7.4.3 Analytical Method .7.4.4 Calculation of PK Parameters .7.5 Implications of PK Parameters on Efficacy .7.5.1 Tissue Samples .7.5.2 PK of Anti TB Drug in granulomas .7.5.3 PK/PD correlations: .7.6 Case Studies (Drugs Administered By Conventional and Pulmonary Routes) .7.6.1 Rifampicin: .7.6.2 Capreomycin .References .8 Drug particle manufacture – Supercritical fluid, high pressure homogenization .8.1 Introduction .8.2 Preparation of nano– and microparticles .8.2.1 Microparticles prepared by a supercritical antisolvent–drug excipient mixing (SAS–DEM)technique .8.2.2 Nnoparticles prepared by a supercritical fluid (SCF) technique .8.2.3 Nanosuspension .8.2.4 Liposomes .References .9 Spray Drying Strategies to Stop Tuberculosis .9.1 Introduction .9.2 Overview of Spray Drying .9.2.1 Advantages of Spray Drying .9.2.2 Hardware .9.2.2.1 Atomisation .9.2.2.1.1 Rotary Atomiser .9.2.2.1.2 Hydraulic or Pressure Nozzles .9.2.2.1.3 Pneumatic Nozzles (Two–Fluid) .9.2.2.2 Drying .9.2.2.2.1 Co–current Flow Dryer .9.2.2.2.2 Counter–current Flow Dryer .9.2.2.2.3 Mixed Flow Dryer .9.2.2.3 Particle Collection .9.2.3 Spray Dryer Classifications .9.2.3.1 Classification Based on the Type of Cycle .9.2.3.1.1 Open Cycle .9.2.3.1.2 Closed Cycle .9.2.3.1.3 Semi–Closed Cycle .9.2.3.2 Classification Based on the Type of Stage .9.2.3.2.1 Single Stage .9.2.3.2.2 Two Stages .9.2.3.2.3 Three Stages .9.2.3.3 Classification Based on the Type of position .9.2.3.3.1 Horizontal .9.2.3.3.2 Vertical .9.2.4 Process Parameters .9.2.4.1 Inlet/Outlet Temperature .9.2.4.2 Drying Gas Airflow Rate .9.2.4.3 Feed Flow Rate .9.2.4.4 Feed Solids Content .9.2.4.5 Ambient Humidity .9.2.4.6 Ambient Temperature .9.2.5 Particle Formation Mechanism .9.3 Advances in Spray Drying Technology .9.3.1 The Quality by Design Approach .9.3.2 The Nano Spray Dryer B–90 .9.3.3 Novel Multi–Channel Nozzles .9.4 Anti–Tuberculosis Therapeutics Produced by Spray Drying .9.4.1 Controlled–Release Microparticles .9.4.1.1 First–Line Drugs .9.4.1.2 Second–Line Drugs .9.4.1.3 Fixed Dose Combinations .9.4.1.4 Adjunct Nitric Oxide .9.4.2 Maximal Drug–loaded Microparticles .9.4.2.1 First–Line Drugs .9.4.2.2 Second–Line Drugs .9.4.2.3 Fixed Dose Combinations .9.4.2.4 Adjunct Pyrazinoate Salts .9.4.2.5 Novel Anti–TB drug Candidate .9.4.3 Vaccines .9.5 Conclusion .Acknowledgements .References .10 Formulation strategies for antitubercular drugs by inhalation .10.1 Introduction .10.2 Lung delivery of TB drugs .10.3 Powders for inhalation and liquids for nebulization .10.4 Antibacterial powders for inhalation: manufacturing of respirable microparticles .10.5 Antibacterial powders for inhalation: devices and delivery strategies .10.6 Conclusions and perspectives .References .11 Inhaled Drug Combinations .11.1 Introduction .11.2 Standard Combinations in Oral and Parenteral Regimens .11.2.1Combinations for the DOTS Regimen .11.3 The Rationale for Inhaled Therapies of TB .11.3.1 Single Drug, Supplementing Other Orally–Administered Drugs .11.3.2 Single Drug Replacing Injectable First– or Second–Line Agents .11.3.3 Multiple Inhaled Drugs, Adjunct or Stand–Alone Therapy .11.3.4 Stimulate the Phagocyte .11.4 Combinations of Anti–TB Drugs with Other Agents .11.4.1 Drugs that Primarily Affect the Pathogen .11.4.2 Drugs that Affect Host Responses .11.4.3 Drugs that Affect Both Host– and Pathogen .11.5 Formulation of inhaled drug combinations .11.5.1 Excipient–Free Formulations .11.5.2 Applications of Excipients .11.5.3 Preparing Multi–Component Particles and Vesicles .11.5.4 Shelf Stability .11.5.5 Drug Release and Pharmacokinetics .11.5.6 Inhalation Dosimetry .11.5 Conclusions .References .12 Ion Pairing For Controlled Drug Delivery .12.1 Introduction .12.2 Ion Pairing Definitions and Concepts .12.2.1 Ion pairing as physicochemical tuning tool .12.2.2 Metal ion complexation .12.2.3 Some considerations on ion pair and metal complex stability .12.3 Ion–Pairs, Complexes and Drug Delivery .12.3.1 Oral route .12.3.2 Transdermal/dermal and mucosal route .12.3.3 Parenteral route .12.3.4 The Pulmonary route and infectious diseases .12.3.4.1 The special case of Tuberculosis .12.3.5 Toxicity considerations .12.4 Remarks .References .13 Understanding the Respiratory Delivery of High Dose Anti–Tubercular Drugs .13.1 Introduction .13.2 Tuberculosis .13.3 Drugs used to Treat Tuberculosis, Doses, Challenges and Requirements for Therapy in Lungs .13.3.1 Current TB Treatment Regimen .13.3.2 Challenges of Conventional Oral and Parenteral Therapy .13.3.3 Rationale for Respiratory Delivery .13.4 Approaches for Respiratory Delivery of Drugs .13.5 Current DPI Formulations and Their Mechanisms of Aerosolization .13.6 Dry Powder Inhaler Formulations for Tuberculosis and Requirements .13.7 Issues to Consider in Respiratory Delivery of Powders for Tuberculosis .13.8 Relationship between De–agglomeration and Tensile strength .13.9 Strategies to improve de–agglomeration: .13.10 DPI Formulations having High Aerosolization .13.11 Devices for High Dose Delivery .13.12 Future Considerations .References .14 Respirable Bacteriophage Aerosols for the Prevention and Treatment of Tuberculosis .14.1 Introduction .14.1.1Bacteriophages .14.1.2 Mycobacteriophages .14.1.3 Mycobacterium tuberculosis as a host for phage infection in vivo .14.1.4 Mycobacteriophages and TB diagnosis .14.2 Treatment or Prevention of Tuberculosis Using Phage–based Agents .14.2.1 Bacteriophages as therapeutic agents .14.2.2 Prospects for using mycobacteriophages for therapy or TB prevention .14.3 Selection of Mycobacteriophages .14.4 Respiratory Drug Delivery of Phages .14.5 Summary and Outlook .References .15 RNA Nanoparticles as Potential Vaccines .15.1 Introduction .15.2 Nanoparticles .15.3 RNA nanoparticle vaccines .15.4 Progression of nanomedicines into the clinic .15.5 The stability problem .15.6 The delivery problem .15.7 RNA as targeting agent or adjuvant? .15.8 Challenges for RNA nanoparticle vaccine characterization .15.9 On the horizon .References .16 Local pulmonary host directed therapies for tuberculosis via aerosol delivery .16.1 Introduction .16.1.1 Tuberculosis disease and control .16.1.2 Chemotherapy and host immunity to tuberculosis .16.1.3 Aerosol delivery of host directed therapies for tuberculosis treatment .16.2 Lung immunity to pulmonary M. tuberculosis infection .16.2.1 Overview .16.2.2 Influence of lung alveoli environment on bacilli survival and its impact on tuberculosis chemotherapy .16.2.3 Potential targets for host directed therapy .16.2.3.1 Potential targets for host directed therapy in macrophage cells .16.2.3.2 Potential targets for host directed therapy in T cells .16.2.3.3 Potential targets for host directed therapy targeting cytokine expression .16.3 Host directed therapies .16.3.1 Previous studies via systemic administration of host directed therapies .16.3.2 Previous studies via aerosol delivery of host directed therapies .16.4 Limitations of preclinical studies to develop inhalational host directed therapies for tuberculosis .16.5 Preclinical testing of inhaled small interference RNA as host directed therapies for tuberculosis .References .17 Treatments for Mycobacterial Persistence and Biofilm Growth .17.1 Introduction .17.2 Mycobacterial Persistence and Drug Tolerance .17.3 Mycobacterial Multi–Cellular Growth .17.4 Mycobacterial Lipids Involved in Biofilm Formation .17.5 Therapies to Treat Mycobacterial Biofilms and Persistence .17.6 Therapies to Treat Mycobacterial Biofilms. The elucidation of pathways important for biofilm .17.7 Conclusion .References .18 Directed Intervention for Immunomodulation against Pulmonary Tuberculosis .18.1 Introduction .18.2 TB Immunology .18.2.1 Early Events of Infection .18.2.2 Delayed Adaptive Immunity .18.2.3 Humoral Immunity and Innate Lymphocytes .18.2.4 Latent Infection .18.2.5 Correlates of protection and tolerance .18.2.6 Natural Immunity against TB infection .18.3 Animal Models of Immunotherapies and Vaccines for TB .18.3.1 Non–human primates .18.3.2 Mouse model .18.4 The Current TB Vaccine– Bacille Calmette Guérin .18.4.1 BCG vaccine history .18.4.2 Failures of BCG .18.4.2.1 Non–tuberculosis mycobacteria .18.4.2.2 BCG Vaccine Antigenicity .18.4.2.3 Mtb strain virulence .18.2.2.4 Helminths .18.5 Other Vaccines Platforms .18.5.1 Live Bacterial Vaccines .18.5.1.1 Safety concerns of live vaccines .18.5.2 Inactivated whole–cell vaccines .18.5.3 Viral vector based TB vaccines .18.5.4 Heterologous prime– boost vaccination strategy in TB .18.6 Pulmonary immunization .18.6.1 Biomimicry: Harnessing natural immunity for protection against TB .18.6.2 Pulmonary Immunization for Global Protection .18.6.3 Safety concerns for pulmonary immunization .18.6.4 Role of adjuvants .18.6.5 Live vs dead vaccines .18.7 Immunotherapeutic Agents against TB .18.7.1 Re–purposed drugs .18.7.2 Vitamin D therapy .18.7.3 Cytokines .18.7.4 Stem cell therapy .18.8 Conclusion .References .19 Clinical and Public Health Perspectives .19.1 Introduction .19.2 Background .19.3 Clinical considerations .19.3.1 Pill burden and fixed dose combinations .19.3.2 Non–adherence and medication monitoring .19.3.3 Intermittent therapy .19.3.4 Drug toxicity .19.3.5 Drug absorption and therapeutic drug monitoring .19.4 Public health considerations .19.4.1 DOTS .19.4.2 Community based therapy .19.4.3 Incentives and Enablers to promote Adherence .19.5 Inhaled drugs and other alternative delivery systems .19.5.1 Possible advantages .19.5.2 Concerns and limitations .19.5.3 Acceptance of novel therapies .19.6 Clinical trials of inhaled injectable drugs .19.6.1 Capreomycin Phase I clinical study .19.6.2 Inhaled therapy to reduce transmission, especially of highly drug resistant strains a trial of inhaled Colistin (or Polymxyin E) .19.7 Other novel delivery strategies .19.8 Pediatric delivery systems .19.9 Conclusion .References .20 Concluding remarks: Prospects and challenges for advancing new drug and vaccine delivery systems into clinical application .20.1 Introduction .20.2 Progress in the formulation and manufacturing of drugs and vaccines for tuberculosis .20.2.1 Inhaled drugs and drug combinations .20.3 Considerations in the development of TB drug and vaccine delivery options .20.3.1 Lung biology and pulmonary administration of drugs and vaccines .20.3.2 Choice of animal model in the evaluation of drug and vaccine delivery systems .20.3.3 Demonstrating bioequivalence and clinical efficacy of inhaled drugs to oral/parenteral dosage forms .20.3.4 Inhaled vaccines for TB are there potential advantages? .20.3.5 Safety of pulmonary vaccination .20.4 Concluding remarks .References .Index
- ISBN: 978-1-118-94317-5
- Editorial: Wiley–Blackwell
- Encuadernacion: Cartoné
- Páginas: 456
- Fecha Publicación: 11/11/2016
- Nº Volúmenes: 1
- Idioma: Inglés