Kooperativer Bibliotheksverbund

UID:

Umfang: Online-Ressource (digital)

ISBN: 9781441902009

Serie: SpringerLink

Inhalt: Recent and rapid progress in the field of biotechnology has resulted in an increasing number of novel macromolecular drugs with great promise for further advanced research and clinical application. However, the delivery of these macromolecular drugs by routes other than the parenteral route is difficult. The pipeline of macromolecular drugs derived from biotechnology presents a challenging opportunity to develop practical dosage forms that could be dosed via the oral route. Given this, the successful oral delivery of macromolecular drugs presents an enormous opportunity. This volume will provide an overview of the innovative oral delivery technologies that have demonstrated success in human testing and will go on to cite the challenges, strategies, and future trends that are to be expected.

Anmerkung: Description based upon print version of record , Oral Delivery of Macromolecular Drugs; Preface; Contents; Contributors; About the Editor; Enzymatic Barriers; 1.1 Introduction; 1.2 The Peptidases; 1.3 The Nucleases; 1.4 Other Enzymes; 1.5 Where Are the Enzymes in the GI Tract?; 1.5.1 The Stomach; 1.5.2 The Lumen of the Small Intestine; 1.5.2.1 Pancreatic Enzymes; 1.5.2.2 Cellular Enzymes; 1.6 Quantitative Aspects of Intestinal Enzymes: How Much and How Active?; 1.7 The Colon; 1.8 The Importance of In Vitro Testing; 1.8.1 Strategies for In Vitro Testing of the Stability of Therapeutic Macromolecules and Macromolecular Formulations , 1.9 ConclusionsReferences; Gastrointestinal Mucus Gel Barrier; 2.1 Introduction; 2.2 Mucin Structural Properties; 2.2.1 Multi-domain Organization; 2.2.1.1 Mucin (O-Glycosylated) Domains; 2.2.1.2 CS-Domains; 2.2.1.3 D-Domains; 2.2.1.4 C- and CK-Domains; 2.2.2 Glycosylation; 2.2.2.1 O-Glycosylation; 2.2.2.2 N-Glycosylation; 2.2.2.3 C-Mannosylation; 2.2.3 Oligomerization/Multimerization; 2.2.4 Molecular Polydispersity; 2.3 Mucin Biosynthesis and Intracellular Processing; 2.3.1 Endoplasmic Reticulum; 2.3.2 Golgi Complex; 2.4 Mucin Intracellular Storage and Secretion; 2.4.1 Mucin Granule , 2.4.2 Mucin Granule Exocytosis2.4.2.1 Regulatory Aspects; 2.4.2.2 Biochemical/Biophysical Aspects; 2.5 Mucin Extracellular Organization; 2.5.1 Mucin Entanglements; 2.5.2 Other Interchain Links; 2.5.3 Mucinases; 2.5.4 Emerging Notion; 2.6 Other Mucus Components; 2.7 Diffusion of Macromolecules in Mucus; 2.7.1 Influence of Mesh Size; 2.7.2 Influence of Other Factors; 2.8 Conclusions; References; The Absorption Barrier; 3.1 Introduction; 3.2 Anatomy of the Digestive Tract; 3.3 Barriers to Transcellular Absorption; 3.3.1 Passive Diffusion; 3.3.2 Transporter Systems; 3.3.3 Pinocytosis , 3.3.4 Transport by Caveolae3.3.5 Efflux Systems; 3.4 Barriers to Paracellular Absorption; 3.4.1 The Tight Junctional Complex; 3.4.2 Modulation of Intestinal Tight Junctions; References; Strategies to Overcome the Enzymatic Barrier; 4.1 Introduction; 4.2 Formulations That Can Protect Drugs from Enzymatic Degradation; 4.3 Chemical Modification; 4.3.1 Modification of N and C Terminus; 4.3.2 Replacement of Labile Amino Acids; 4.3.3 PEGylation; 4.4 Enzyme Inhibitors; 4.4.1 Protease Inhibitors Which Are Not Based on Amino Acids , 4.4.2 Protease Inhibitors Which Are Based on Amino Acids and Modified Amino Acids4.4.3 Protease Inhibitors Which Are Based on Peptides and Modified Peptides; 4.4.4 Protease Inhibitors Which Are Based on Polypeptides; 4.4.5 Protease Inhibitors That Can Complex Ions; 4.4.6 Protease Inhibitors Based on Multifunctional Mucoadhesive Polymers; 4.4.6.1 Poly(acrylates); 4.4.6.2 Thiolated Polymers; 4.4.6.3 Polymer-Enzyme Inhibitor Conjugates; 4.5 Conclusion and Future Trends; References; Low Molecular Mass Permeation Enhancers in Oral Delivery of Macromolecular Drugs; 5.1 Introduction , 5.2 Transcellular Permeation Enhancers

Weitere Ausg.: ISBN 9781441901996

Weitere Ausg.: Buchausg. u.d.T. ISBN 978-1-441-90199-6

Sprache: Englisch

DOI: 10.1007/978-1-4419-0200-9

URL: Volltext

URL: Volltext  (lizenzpflichtig)

URL: Cover

UID:

Umfang: XIII, 242 p. , online resource.

Ausgabe: 1st ed. 2009.

ISBN: 9781441902009

Inhalt: Due to a rapid development in biotechnology more and more macromolecular drugs such as therapeutic peptides, oligosaccharides and nucleic acids are entering the pharmaceutical arena representing unprecedented challenges from the drug delivery point of view. One of the likely greatest challenges is their oral administration presenting a series of attractive advantages. Oral Delivery of Macromolecular Drugs addresses the most critical issues for a successful oral delivery of macromolecular drugs by a detailed characterisation of the 'enemy's strength' which is mainly based on the enzymatic barrier, the mucus gel barrier and the absorption barrier. Each of these barriers is described in detail in separate chapters by leading scientists in the field. The higher the knowledge about these barriers, the more potent oral macromolecular delivery systems can be generated. In the second part of this volume an overview on the likely most promising strategies to overcome these barriers is provided. Each of these strategies is described in detail in chapters being authored by worldwide academic and industrial experts. These strategies include the use of auxiliary agents such as polymeric and low molecular mass permeation enhancers, efflux pump inhibitors and enzyme inhibitors. Furthermore, these strategies are based on delivery systems such as liposomal formulations and micro- and nanoparticles. Oral Delivery of Macromolecular Drugs provides also an overview on special topics in oral macromolecular drug delivery such as oral immunization and gene delivery. Each of these chapters benefits from the results of various in vivo studies demonstrating the potential of discussed delivery systems. On the one hand macromolecular drugs can be produced more and more effectively making also low oral bioavailabilities in the range of 0.5 - 5% commercially interesting. On the other hand, oral macromolecular drug formulations are becoming more and more efficient. Taking these developments into consideration, the number of oral macromolecular delivery systems entering the market will increase considerably over the years. 'Invasive-to-oral-conversions' promise great rewards for those investing in this market. Oral Delivery of Macromolecular Drugs should encourage and motivate scientists in academia and industry to move in or intensively their activities in this challenging research field of great future. About the Editor Andreas Bernkop-Schnürch is the Dean of the Faculty of Chemistry and Pharmacy and Professor of Pharmaceutical Technology at the University of Innsbruck, Austria. His main interests focus on non-invasive drug delivery systems, multifunctional polymers such as thiomers, mucoadhesion and permeation enhancement. He is author of more than 200 original research and review articles and received the Research-Award of the City of Vienna (Vienna), EURAND-Award (Boston), Best of Biotech Award (Vienna), MBPW-Award (Munich), PHÖNIX Award (Mannheim), Houska-Award (Vienna) and Austrian-Nanoaward (Vienna). In addition, Andreas Bernkop-Schnürch is founder and owner of the following companies: ThioMatrix GmbH, Dr. K. Schnürch KG and Green River Polymers GmbH.

Anmerkung: Enzymatic Barriers -- Gastrointestinal Mucus Gel Barrier -- The Absorption Barrier -- Strategies to Overcome the Enzymatic Barrier -- Low Molecular Mass Permeation Enhancers in Oral Delivery of Macromolecular Drugs -- Polymeric Permeation Enhancers -- Strategies to Overcome Efflux Pumps -- Multifunctional Polymeric Excipients in Oral Macromolecular Drug Delivery -- Nano- and Microparticles in Oral Delivery of Macromolecular Drugs -- Liposome-Based Mucoadhesive Formulations for Oral Delivery of Macromolecules -- Strategies in Oral Immunization -- Oral Delivery of Nucleic Acid Drugs.

In: Springer Nature eBook

Weitere Ausg.: Printed edition: ISBN 9781441902016

Weitere Ausg.: Printed edition: ISBN 9781441901996

Weitere Ausg.: Printed edition: ISBN 9781489982827

Sprache: Englisch

DOI: 10.1007/978-1-4419-0200-9

URL: https://doi.org/10.1007/978-1-4419-0200-9