Role of Lipid Excipients in Modifying Oral and Parenteral Drug Delivery: Basic Principles and Biological Examples

Cover......Page 1
Title......Page 2
Publisher......Page 6
Contents......Page 7
Preface......Page 8
Contributors......Page 10
1.1 INTRODUCTION......Page 12
1.2 INTESTINAL ABSORPTIVE TRANSPORTERS......Page 14
1.2.1 ASBT (SLC10A2)......Page 15
1.2.2 PEPT1 (SLC15A1)......Page 16
1.2.4 MCT1 (SLC16A)......Page 17
1.2.6 ENT and CNT (SLC29A and SLC28A)......Page 18
1.3 INTESTINAL EFFLUX TRANSPORTERS......Page 19
1.3.1 MDR1 (ABCB1)......Page 22
1.3.3 BCRP (ABCG2)......Page 24
1.3.4 ABCG5/G8 and ABCA1......Page 25
1.4 MODULATION OF DRUG TRANSPORTERS BY EXCIPIENTS AND SURFACTANTS......Page 26
1.5 CONCLUSION......Page 29
REFERENCES......Page 30
2.1 INTRODUCTION......Page 43
2.2 LIPIDS FOR DRUG DELIVERY APPLICATIONS......Page 44
2.3 MECHANISMS OF IMPROVEDORAL BIOAVAILABILITY......Page 45
2.4 LIPID-BASED DRUG DELIVERY FORMULATIONS......Page 46
2.4.2 Dry Emulsions......Page 47
2.4.4 Fat Emulsions......Page 48
2.4.6 Liposomes......Page 49
2.4.7 Lipid-based Micelles......Page 51
REFERENCES......Page 54
3.1 INTRODUCTION......Page 59
3.2.1 Liposomes......Page 60
3.2.3 Long-circulating Liposomes......Page 62
3.3.1 Immunotargeting......Page 63
3.3.4 Other Targeting Ligands......Page 64
3.3.6 The pH-sensitive Liposomes......Page 65
3.3.7 Intracellular Targeting......Page 66
3.4.1 Protein and Peptide Drugs......Page 67
3.4.2 Liposomal Enzymes and Proteins......Page 69
3.4.3 Liposomal Peptides......Page 72
3.4.4 Liposomal ATP......Page 73
3.4.5 Liposomes as Adjuvants......Page 74
3.5.2 Micelles and Micellization......Page 75
3.5.3 Polymeric Micelles......Page 76
3.5.4 Lipid-core Micelles......Page 77
3.5.5 Drug-loaded Micelles......Page 78
3.5.6 ‘Passive’ Micelle Targeting......Page 79
3.5.7 Ligand-targeted Micelles......Page 81
3.5.8 Lipid-core Micelles for Intracellular Drug Delivery......Page 82
REFERENCES......Page 83
4.1 INTRODUCTION......Page 99
4.2 EMULSION STABILITY......Page 101
4.2.1 Destabilization Processes......Page 102
4.2.2 Electrostatic Stabilization......Page 103
4.3.1 Lipid Emulsions Metabolized as Endogenous Chylomicrons......Page 105
4.3.2 Elimination by the Mononuclear Phagocyte System......Page 106
4.4.1 Effect of Lipid Emulsion Size......Page 107
Composition of the Oil Phase......Page 110
4.4.3 Effect of Surface Charge......Page 111
Sphingomyelin......Page 112
Polyethyleneglycol Lipids......Page 114
4.4.5 Active Targeting of Selected Cells......Page 115
Antibody–peptide Conjugation onto Long-circulating Lipid Emulsions......Page 117
Internal Phase (Oils)......Page 119
Emulsifiers......Page 121
Aqueous Phase......Page 123
4.5.2 Emulsion Preparation......Page 124
4.5.3 Emulsion Characterization......Page 125
Physical Stability......Page 126
4.6 LIPID EMULSIONS FOR THE DELIVERY OF NUCLEIC ACID-BASED DRUGS......Page 127
4.7 CONCLUSION......Page 128
REFERENCES......Page 129
5.1 INTRODUCTION......Page 135
5.2 CONCEPT OF DIFFERENTIAL PROTEIN ADSORPTION......Page 137
5.3.1 2-DE Analysis......Page 138
Separation Problem......Page 139
Adsorption Kinetics......Page 142
Serum versus Plasma......Page 147
5.4.1 Influence of Lipid Composition of o/w Emulsions onProtein Adsorption......Page 150
5.4.2 Influence of Surface Modification of o/w Emulsions on Protein Adsorption......Page 152
5.4.3 Influence of Drug Loading of o/w Emulsions on Protein Adsorption......Page 155
5.4.4 Physiological Stability of o/w Emulsions......Page 156
5.5.1 Influence of the Matrix Lipid of SLNs on Protein Adsorption......Page 158
5.5.2 Influence of Surface Modification of SLNs on Protein Adsorption......Page 160
5.6 CONCLUSION......Page 162
REFERENCES......Page 165
6.1 INTRODUCTION TO DRUG DELIVERY......Page 171
6.2 NANOPARTICLES AS A CURRENT DELIVERY SYSTEM......Page 172
6.2.1 Design......Page 173
6.3 THE IMPORTANCE OF SPECIFICITY......Page 174
6.3.1 Nanoparticle Drug Delivery to the Brain......Page 175
6.3.2 Cancer Therapy......Page 177
6.4 DISCUSSION......Page 178
REFERENCES......Page 179
7.1 INTRODUCTION......Page 181
7.2.1 Ultrasound Contrast Agents......Page 182
7.3.1 Backscatter......Page 184
7.3.2 Cavitation of Bubbles......Page 185
7.3.3 Radiation Force/Microstreaming......Page 186
7.4.2 LPSs as Therapeutic Agents for Ultrasound-mediated Sonothrombolysis of Vascular Thrombi......Page 187
7.4.3 Research and Thrombosis......Page 188
7.4.4 Bubble-Assisted Sonothrombolysis – Clinical Studies......Page 190
7.4.5 Targeted LPSs......Page 193
7.4.7 Liquid PFC-filled Targeted LPSs as Ultrasound-mediated Drug Delivery Agents......Page 199
7.5 OXYGEN DELIVERY......Page 202
REFERENCES......Page 204
INDEX......Page 208
Back Cover......Page 217