Pharmaceutical Biotechnology, Second Edition

by Groves; Michael J.

• ISBN13: 9780849318733
• ISBN10: 0849318734
• Edition: 2nd
• Format: Hardcover
• Copyright: 2005-08-29
• Publisher: CRC Press

Summary

Since the publication of the first edition of Pharmaceutical Biotechnology over a decade ago, a not-so-subtle shift in the meaning of the term "biotechnology" has occurred. It has come to mean something very specific, namely the development of drug substances with large protein and polypeptide molecules. These substances can be used as drugs in their own right but may also be used to manipulate cellular DNA in order to produce a required molecule that is believed to have desirable properties in the treatment of a disease. Accordingly, the second edition of this popular text reflects that change of definition by including new material that explores the development of these protein-based therapeutic substances.See what's new in the Second Edition:· Expanded coverage of the formulation of proteins· Additional information on proteins used as drug delivery systems· Detailed discussion of interactions between proteins and phospholipids· Increased information on proteomics and gene therapy· Exploration of pulmonary administration and oral delivery of proteins· A broad review of vaccines· Discussion of genetic engineering and genomics· Challenges and issues involved in the development and the production of a drug

Table of Contents

Chapter 1 Introduction	1	(4)
Michael J. Groves
Chapter 2 Proteins	5	(26)
Charles P. Woodbury, Jr.
Protein Structure	5	(9)
Classification of Proteins	5	(1)
Amino Acids	6	(1)
Primary Protein Structure	7	(2)
Protein Secondary Structure	9	(3)
Tertiary and Quaternary Structure in Globular Proteins	12	(2)
Protein Biosynthesis	14	(7)
Messenger RNA and RNA Polymerase	14	(2)
mRNA Processing	16	(1)
The Genetic Code	17	(1)
Activated Amino Acids and Transfer RNA	18	(1)
The Ribosome and Associated Factors	19	(1)
Message Translation and Protein Synthesis	20	(1)
Protein Modification	21	(1)
Types of Modification	21	(1)
Protein Transport and Modification	22	(1)
Protein Stability	22	(7)
The Importance of Noncovalent Interactions	22	(1)
Types of Noncovalent Interactions	23	(2)
The Hydrophobic Effect	25	(1)
Protein Folding and Noncovalent Interactions	26	(1)
Thermodynamics and Kinetics of Protein Folding	27	(2)
Further Reading	29	(2)
Chapter 3 Recombinant DNA Basics	31	(30)
Charles P. Woodbury, Jr.
The Uses of Recombinant DNA	31	(1)
Gel Electrophoresis	32	(2)
Nucleic Acid Hybridization Assays	34	(6)
DNA Structure and Complementary Base Pairing	34	(1)
DNA Renaturation, Annealing, and Hybridization	35	(1)
Hybridization Assays	36	(4)
The Polymerase Chain Reaction	40	(4)
Templates, Primers, and DNA Polymerase	41	(1)
The PCR Amplification Process	42	(1)
Applications of PCR	43	(1)
Constructing Recombinant DNA Molecules	44	(11)
DNA Clones	44	(2)
Sources of DNA for Cloning	44	(2)
Cutting and Joining DNA	46	(3)
DNA Vectors	49	(2)
Host Cells for Recombinant DNA Work	51	(1)
Methods for Screening and Selecting Transformants	52	(2)
Expression of Foreign Genes	54	(1)
Engineering Protein Sequences	55	(1)
Site-Directed Mutagenesis	55	(1)
Examples of Applied Recombinant DNA Technology	56	(3)
Cloning of Human Somatostatin in E. coli	57	(1)
Engineering Bacteria for Industrial Production of Valuable Small Organics	57	(1)
Cloning Receptors in Bacteria	58	(1)
Further Reading	59	(2)
Chapter 4 Monoclonal Antibodies	61	(22)
David J. Groves
What Are Monoclonal Antibodies?	61	(2)
Applications of Monoclonal Antibodies	63	(5)
Diagnosis	64	(1)
Imaging	65	(1)
Therapy	66	(2)
Purification and Other Applications	68	(1)
The Generation of Monoclonal Antibodies	68	(7)
Immunization	68	(3)
Myelomas	71	(1)
Cell Fusion	72	(1)
Screening Assays	73	(1)
Cloning	73	(1)
Cell Line Characterization	74	(1)
Antibody Characterization	75	(1)
Genetic Engineering	75	(4)
Recombinant Antibodies—Humanization and Deimmunization	75	(2)
Antibody Fragments and Constructs	77	(2)
Transgenic Mice	79	(1)
Production Methods	79	(3)
In Vivo Production	79	(1)
Mammalian Cell Culture	79	(2)
Bacterial Cell Culture	81	(1)
Transgenic Animals	81	(1)
Transgenic Plants	81	(1)
Pharmaceutical, Regulatory, and Commercial Aspects	82	(1)
Pharmaceutical Regulation	82	(1)
Further Reading and Websites	82	(1)
Chapter 5 Proteomics: A New Emerging Area of Biotechnology	83	(64)
N.O. Sahin
Introduction	84	(1)
What Is a Proteome?	85	(2)
Technologíes for Proteomics	87	(2)
Protein Identification	89	(31)
ID-SDS-PAGE	91	(1)
2-DE	92	(12)
Historical Development of 2-DE	92	(1)
Steps of 2-DE	92	(5)
Resolution of 2-DE Gels	97	(1)
Reproducibility of Protein Profiles Obtained by 2-DE	97	(1)
Stains and Dyes of 2-DE	97	(5)
Image Analysis in 2-DE	102	(1)
Drawbacks of 2-DE/SDS-PAGE	103	(1)
Isoelectric Focusing (IEF)	104	(1)
High Performance Liquid Chromatography	104	(1)
Capillary Electrophoresis	105	(1)
Protein Digestion	105	(1)
Mass Spectrometry (MS) for Proteomics	106	(3)
MALDI-TOFF	107	(1)
ESI Tandem MS	108	(1)
Techniques Used for Structural Proteomics	109	(1)
X-Ray Crystallography	110	(1)
Drawbacks of X-Ray Crystallography	111	(1)
Nuclear Magnetic Resonance	111	(1)
Phage Display Technique for Functional Proteomics	112	(15)
Fields of Application for Phage Display Technique	119	(1)
Bioinformatics	120	(7)
DNA and Protein Microarray Technologies	127	(6)
DNA Arrays	128	(2)
Design of a Microarray System	129	(1)
Attachment of a Single DNA Molecule to a Silicon Suíface	129	(1)
How to Choose an Array	130	(1)
Protein Arrays	130	(1)
Applications of DNA and Protein Microarray Technology	131	(2)
Pharmaceutical and Medical Applications of Proteomics	133	(4)
Conclusions	137	(2)
References and Further Reading	139	(8)
Chapter 6 Commonly Used Analytical Techniques for Biotechnology Products	147	(32)
Wei Tang and Kadriye Ciftci
Analytical Tools for Proteins	148	(1)
Spectroscopic and Photometric Methods	148	(9)
Ultraviolet-Visible (UV-VIS)	148	(1)
Infrared Spectroscopy	149	(1)
Raman Spectroscopy	150	(1)
Atomic Absorption (AA) Spectrophotometry	150	(1)
Mass Spectrometry (MS)	151	(2)
Nuclear Magnetic Resonance Spectroscopy (NMR)	153	(1)
Electron Spin Resonance	154	(1)
Optical Rotary Dispersion and Circular Dichroism Spectroscopy	154	(1)
Fluorescence Spectroscopy	155	(1)
Chemiluminescence and Bioluminescence	155	(1)
X-Ray Crystallography	156	(1)
Dynamic Light Scattering	156	(1)
Other Methods	157	(1)
Differential Scanning Calorimetry (DSC)	157	(1)
Chromatographic Methods	157	(8)
Adsorption Chromatography	158	(1)
Gas-liquid Chromatography (GLC)	158	(1)
Partition Chromatography	159	(1)
Ion Exchange Chromatography	160	(1)
Size-exclusion Chromatography (SEC)	161	(2)
Affinity Chromatography	163	(1)
High-Performance Liquid Chromatography	164	(1)
Electrophoresis	165	(3)
Bioassays	168	(6)
Immunoprecipitation	168	(1)
Complement Assay	169	(2)
Agglutination	171	(1)
Enzyme Immunoassay (EI)	171	(2)
Radio Immunoassay	173	(1)
References	174	(5)
Chapter 7 Formulation of Proteins and Peptides	179	(36)
Michael J. Groves
Introduction	180	(1)
Making Small Protein Particles: Precipitation of Proteins from Supercritical Fluids	181	(1)
Parenteral Drug Delivery Systems	181	(13)
General Introduction	181	(1)
Heat Sterilization	182	(1)
Bacterial Death	183	(3)
Sterilization Methods	186	(6)
Moist Heat	186	(1)
Dry Heat	186	(1)
Sterilizing Gases	187	(1)
Ionizing Radiation	187	(1)
Sterile Filtration	188	(2)
The Concept of "Size" as Related to a Filtration Process	190	(1)
Aseptic Assembly	190	(2)
Quality Control Issues	192	(1)
Lyophilization (Freeze-Drying)	193	(1)
Drug Delivery through the Skin	194	(4)
Skin	194	(4)
Iontophoresis	198	(1)
Multiphase Drug Delivery Systems	198	(3)
Microemulsions	198	(5)
Microemulsions as Particulate Systems	201	(1)
Spontaneous Microemulsion Formation	201	(1)
Protein Compaction	201	(2)
Self-Emulsifying Drug Delivery Systems	203	(4)
Evaluation of SEDDS Performance Parameters	204	(1)
Selection of Components for a SEDDS	205	(1)
Possible Mechanisms for the Formation of Self-Emulsified Emulsions	206	(1)
Inclusion Compounds and Cyclodextrins as Delivery Systems	207	(5)
References and Further Reading	212	(3)
Chapter 8 Proteins as Drug Delivery Systems	215	(26)
Michael J. Groves
Introduction	215	(1)
Collagen	216	(1)
Gelatin	216	(19)
The Origins and Constitution of Gelatin	216	(2)
Phase Relationships of Gelatin Systems	218	(2)
The Preparation of Gelatin Particles	220	(8)
Emulsification Processes	221	(1)
Precipitation Processes	221	(7)
Submicron Diameter Gelatin Particles	228	(1)
Gelatin Precipitation	228	(4)
Optimization of Gelatin Nanoparticle Production	232	(1)
The Toxicity of Gelatin	233	(1)
Sterilization of Gelatin Products	233	(1)
Tissue Targeting with Gelatin Microparticles	234	(1)
Albumin Microparticles	235	(3)
Introduction	235	(1)
Albumin Microparticles	236	(11)
Emulsification Processes	236	(1)
Atomization Processes	237	(1)
Properties of the Particles	238	(1)
References and Further Reading	238	(3)
Chapter 9 Proteins and Phospholipids	241	(18)
Michael J. Groves
Introduction	241	(1)
Structural Properties of Phospholipids	241	(3)
Injectable Lipid Emulsions	244	(1)
Formulation and Preparation	244	(3)
The Physical State of Phospholipids-Stabilized Emulsions	247	(7)
Injectable Emulsions as Drug Delivery Systems	247	(1)
Liposomes	248	(37)
Charged Liposomes	250	(1)
Surface-Modified Liposomes	251	(1)
Direct Interactions between Proteins and Liposomes	251	(3)
Peptides and Phospholipids	254	(2)
Cochleal Phospholipid Structures	256	(1)
References and Further Reading	256	(3)
Chapter 10 Pulmonary Drug Delivery Systems for Biomacromolecules	259	(24)
Camellia Zamiri and Richard A. Gemeinhart
The Pulmonary Route of Drug Delivery	259	(1)
Anatomy and Physiology of the Respiratory System	260	(3)
Lipid-Based Pulmonary Delivery	263	(4)
Solid Colloidal Particles	267	(1)
Poly(dl-lactide-co-glycolide)	267	(2)
Polycyanoacrylates	269	(1)
Gelatin	270	(1)
Poly(ether-anhydrides)	271	(1)
Diketopiperazine Derivatives	272	(1)
Polyethyleneimine (PEI)-DNA Complexes	272	(1)
Poly(ethylene glycol) Conjugates	273	(1)
Factors Affecting Pulmonary Dosing	274	(3)
Conclusions	277	(1)
References and Further Reading	278	(5)
Chapter 11 Polymeric Systems for Oral Protein and Peptide Delivery	283	(24)
Richard A. Gemeinhart
Introduction	283	(2)
Polymers Used for Controlled Drug Delivery	285	(16)
Hydrophobic Polymers	285	(10)
Poly(esters)	286	(4)
Poly(cyanoacrylate)	290	(2)
Poly(ortho esters)	292	(2)
Poly(phosphazenes)	294	(1)
Hydrophilic Polymers	295	(13)
Polymer-Protease Inhibitor Conjugates	295	(2)
Poly(alkyl methacrylates)	297	(1)
Poly(methacrylates) and Poly(acrylates)	298	(1)
Alginates	299	(1)
Chitosan	300	(1)
Polyphosphazene Hydrogels	301	(1)
Poly(ethylene glycol) or Poly(ethylene oxide)	301	(1)
Conclusions	301	(1)
References and Further Reading	302	(5)
Chapter 12 Vaccines: Ancient Medicines to Modern Therapeutics	307	(26)
K.O. Alpar and Michael J. Groves
Introduction	308	(3)
A Brief History of Vaccine Development	308	(1)
BCG—The Only Tuberculosis Vaccine	309	(2)
Requirements of an Ideal Vaccine for Today	311	(1)
Types of Modern Vaccines	312	(3)
Attenuated Live Vaccines	313	(1)
Killed Inactivated Vaccines	313	(1)
Conjugate Vaccines	314	(1)
Subunit Vaccines	314	(1)
Emerging Vaccine Types	315	(2)
Protein Vaccines	315	(1)
DNA Vaccines	315	(1)
Lipid and Carbohydrate Antigen Vaccines	316	(1)
Recombinant Live Carriers	316	(1)
The Immune System and Mechanisms of Action	317	(3)
Antigens	318	(1)
Antibodies	318	(1)
Immunoglobulins	318	(1)
T-Cell Receptors	319	(1)
Major Histocompatibility Complex (MHC)	319	(1)
Types of Immune Defense Mechanisms	320	(1)
The Mucosal System	321	(3)
Associated Lymphoid Tissues	322	(1)
Mucosal-Associated Lymphoid Tissues	322	(2)
Vaccine Adjuvants	324	(2)
Modern Microparticulate Vaccine Vehicles	326	(3)
Biodegradable Polymers	326	(1)
Lipid Particles as Adjuvants and Delivery Systems	327	(1)
Chitosans	328	(1)
The Future of Vaccines and Vaccination	329	(3)
Some Future Vaccine Opportunities	331	(1)
Risk-Benefit Ratios	331	(1)
References and Further Reading	332	(1)
Chapter 13 Gene Therapy: An Overview of the Current Viral and Nonviral Vectors	333	(46)
Kadriye Ciftci and Anshul Gupte
Introduction	333	(4)
Gene Delivery Systems	337	(28)
Viral Vectors	337	(8)
Retroviruses	337	(2)
Adenoviruses	339	(3)
Adeno-Associated Viruses	342	(1)
Other Viruses	343	(2)
Nonviral Vectors	345	(17)
Direct Injection of Naked DNA	348	(1)
Liposomes	349	(4)
Polymers	353	(5)
Receptor-Mediated Gene Delivery	358	(1)
Hybrid Vectors (Viral and Nonviral Components)	359	(1)
Nuclear Localization Signal Peptides and Membrane-Modifying Agents	360	(1)
Membrane-Modifying Agents	361	(1)
Electroporation	362	(3)
References	365	(14)
Chapter 14 Regulatory and Compendial Issues	379	(10)
Michael J. Groves
Introduction	379	(1)
The FDA	380	(4)
Origins and Organization	380	(1)
Good Manufacturing Practices and the Inspection Process	381	(2)
The Review Process	383	(1)
The United States Pharmacopeia	384	(5)
Origins and Organization	384	(2)
Format	386	(1)
Harmonization	387	(2)
Chapter 15 Some Challeges Relating to the Future of Biopharmaceutical Technology	389	(8)
Michael J. Groves
Introduction	389	(1)
Examples of Essential Biopharmaceuticals	390	(1)
Insulin	390	(1)
Growth Hormone	390	(1)
Interferon β 1a	391	(1)
Other Expensive Drug Therapies	391	(1)
Pharmacoeconomics and Value for Money	391	(2)
Generic Biotechnological Drug Issues	393	(1)
Alternatives to Protein Biologics	394	(1)
Gene Engineering	394	(1)
Conclusions	395	(1)
Acknowledgments	396	(1)
References	396	(1)
Index	397