Comprehensive resource presenting state-of-the-art of membrane emulsification technology, from principle to practice, with focus on biomedical applications
Novel Membrane Emulsification: Principles, Preparation, Processes, and Bioapplications provides comprehensive coverage of membrane emulsification technology by summarizing the principle, preparation, and bioapplications through utilizing uniform particle size, introducing recent development in preparation and applications in the controlled release and delivery of protein/peptide, anticancer drugs and vaccines, and in the bioseparation media and cell culture carriers, and discussing direct, rapid, and rotary membrane emulsification equipments.
Novel Membrane Emulsification includes information on: - Preparation of hydrophobic microspheres from O/W emulsion, hydrophilic microspheres from W/O emulsion, and microcapsules/composite microspheres from double emulsions, covering preparation from monomer and preformed polymer systems - Preparation of small particles by rapid membrane emulsification process - Applications of uniform particles in sustained release of protein/peptide drugs, covering strategies to improve encapsulation efficiency and maintain bioactivity of drugs - Applications of uniform particles in anticancer drug and vaccine delivery including personalized therapeutic vaccine - Applications of uniform particles in protein separation, covering uniform agarose microsphere for protein separation and super-porous microsphere for vaccine separation
Novel Membrane Emulsification is an essential resource for scientists and researchers in multiple fields, particularly chemistry, chemical engineering, and materials science, to advance this technique and produce novel materials with controlled characteristics. The text is also a valuable learning resource for biomedical science and bioengineering researchers and students.
Table of Contents
Preface xv
1 Membrane Emulsification Process: Principle and Model 1
1.1 Introduction 1
1.2 Cross-Flow Membrane Emulsification 2
1.2.1 Mechanism of Droplet Formation 2
1.2.2 Force Balance Model 6
1.2.3 Torque Balance Model 8
1.2.3.1 Associating the Dispersed-Phase Parameters 9
1.2.3.2 Associating the Continuous Phase Parameters 10
1.2.3.3 Torque Balance Model Associating Operation Parameters 10
1.2.3.4 Evaluation of Controlling Factors on Droplets Uniformity by Torque Balance Model 11
1.2.4 Computational Fluid Dynamics 16
1.2.5 Models by Surface Evolver Tool 19
1.2.6 Models by Lattice Boltzmann Method 20
1.3 Premix Membrane Emulsification 21
1.4 Summary 23
References 23
2 Preparation of Hydrophobic Microspheres From O/W Emulsion 27
2.1 Introduction 27
2.2 Preparation from Monomer System 28
2.2.1 PST-DVB Microspheres 28
2.2.2 PST-DMAEMA Microspheres 29
2.2.3 PGMA Microspheres 31
2.2.4 PST-HEMA Microspheres 32
2.2.5 PMMA Microspheres 34
2.3 Preparation from Performed Polymer System 37
2.3.1 PST-PMMA Microspheres 37
2.3.2 Polyurethane Urea Microspheres 39
2.3.3 Polyimide Prepolymer (PIP) Microspheres 40
2.3.4 Biodegradable Poly(Lactide) Microspheres 41
2.3.5 Microcapsules Containing Inorganic Materials 43
2.3.6 Pickering Emulsion 43
2.4 Morphology Control of Microspheres 45
2.4.1 Effect of Crosslinker on Morphology of Microspheres 45
2.4.2 Effect of Inert Diluents on Morphology of Microspheres 46
2.4.2.1 Nonsolvating Diluent Effects on Microsphere Morphology 47
2.4.2.2 Solvating Diluent Effects on Microsphere Morphology 49
2.4.3 Effect of Emulsifier/Stabilizer on Morphology of Microspheres 52
2.4.4 Effect of Cosurfactant on Morphology of Composite Microspheres 52
2.5 Summary 56
References 57
3 Preparation of Hydrophilic Polymer Microspheres from W/O Emulsion 61
3.1 Introduction 61
3.2 Membrane Modification and Preparation 62
3.2.1 Hydrophobic Modification of the Membrane 62
3.2.2 Preparation of Hydrophobic Membrane 67
3.3 Preparation Microparticles from Monomer System 73
3.3.1 Preparation of Poly(N-isopropylacrylamide) (PNIPAM) Microspheres and Microcapsules 73
3.4 Preparation Microparticles from Preformed Polymer System 77
3.4.1 Chitosan Microspheres 77
3.4.2 Agarose Microspheres 83
3.4.3 Alginate Microspheres 89
3.4.4 Cellulose Microspheres 93
3.4.5 Glucomannan Microspheres 94
3.5 Other Hydrophilic Microspheres Prepared by Membrane Emulsification 95
3.5.1 PVA Microspheres 95
3.5.2 Protein Microspheres 98
3.6 Summary 99
References 100
4 Preparation of Uniform Microcapsules and Microspheres from W/O/W Double Emulsion 105
4.1 Introduction 105
4.2 Preparation of Uniform Microcapsules 107
4.2.1 Oil-Soluble Emulsifier on the Size Distribution of Microcapsules 109
4.2.2 PVA Concentration in the Outer Aqueous Phase 110
4.2.3 Transmembrane Pressure on the Size Distribution of Microcapsules 110
4.2.4 The Membrane with Different Pore Size 112
4.2.5 Microcapsules for Drug Encapsulation 113
4.2.5.1 Composition of Polymers 113
4.2.5.2 The Inner Aqueous Phase Volume 114
4.2.5.3 NaCl Concentration in Outer Aqueous Phase 115
4.2.5.4 Drug-Loading Amount 116
4.2.5.5 pH Value in Outer Aqueous Phase 117
4.2.5.6 Microcapsules Size 117
4.2.6 Microcapsules with Controllable Structure 119
4.2.6.1 Polymer Concentrations in Oil Phase 119
4.2.6.2 Solidification Rate of the Droplets 119
4.2.6.3 Stabilizer Type 121
4.2.6.4 Volume Fraction of the Inner Aqueous Phase 121
4.3 Preparation of Composite Microspheres 121
4.3.1 Water-Soluble Inhibitor 123
4.3.2 Stabilizer in Outer Aqueous Phase 123
4.3.3 Cross-Linking Agent 124
4.4 Summary 126
References 126
5 Rapid Membrane Emulsification Process for Preparation of Small Microspheres 129
5.1 Introduction 129
5.2 Preparation of Hydrophobic Microspheres from O/W Emulsion 130
5.2.1 Preparation of Polylactide-Based Particles from O/W Emulsion 130
5.2.2 Preparation of PST Particles from O/W Emulsion 132
5.2.3 Preparation of Drug-Loaded Particles from O/W Emulsion 132
5.2.3.1 Preparation of Drug-Loaded Particles via Adsorption 133
5.2.3.2 Preparation of Drug-Loaded Particles via Encapsulation 133
5.2.3.3 Preparation of Polydopamine Microcapsules 135
5.3 Preparation of Hydrophilic Microspheres from W/O Emulsion 136
5.3.1 Preparation of Chitosan Particles 136
5.3.1.1 Preparation of Chitosan Solid Particles 136
5.3.1.2 Preparation of Chitosan gel Particles 138
5.3.2 Preparation of Stimuli-Responsive PNIPAM Particles 139
5.3.3 Preparation of Agarose Particles 139
5.3.4 Preparation of Alginate Particles 141
5.3.5 Preparation of Konjac Glucomannan Particles 143
5.4 Preparation of Microcapsule from Double Emulsion 144
5.4.1 Preparation of Drug/Antigen-Loaded Microcapsules via W/O/W Emulsions 144
5.4.1.1 Preparation of Particles for Encapsulating Water-Soluble Antigen 144
5.4.1.2 Preparation of Particles for Encapsulating Water-Soluble Drugs 145
5.4.1.3 Preparation of Hollow Particles for Encapsulating Antigen/Drug 147
5.4.2 Preparation of Microspheres with Unique Structure via W/O/W Emulsion 147
5.4.2.1 Preparation of PLA/PLGA Microspheres with Single-Core Structure 147
5.4.2.2 Preparation of PMMA/PLGA Microspheres with Gigaporous Structures 149
5.4.2.3 Preparation of PLGA Microspheres with Nonspherical Structures 151
5.4.3 Preparation of Microspheres via O/W/O Emulsion 152
5.4.3.1 HTCC Chitosan Microspheres for Oral Administration via O/W/O 153
5.4.3.2 CMCC Chitosan Microspheres for Encapsulating Water-Insoluble Drugs 154
5.4.3.3 Chitosan Microspheres for Combined Drug Delivery and Specific Administration 155
5.4.3.4 Preparation of Biomimetic Chitosan Microsphere with Cell Membrane 157
5.5 Summary 158
References 158
6 Applications of Uniform Particles in Sustained Release of Drugs 163
6.1 Introduction 163
6.2 Synthetic Polymer (PLA, PLGA, and PELA) 164
6.2.1 Pla 164
6.2.2 Plga 166
6.2.3 Pela 167
6.2.4 Strategy to Improve Encapsulation Efficiency 168
6.2.4.1 Effect of Additives on Encapsulation Efficiency 168
6.2.4.2 Effect of pH in the External Phase 169
6.2.4.3 Effect of Polymer 170
6.2.4.4 Effect of Solidification Technique 171
6.2.4.5 Using Post-loading Mode Instead of Pre-loading Mode 174
6.2.5 Strategy to Maintain Bioactivity of Drugs 175
6.2.5.1 Adding Additives to Prevent Proteins from Denaturation 175
6.2.5.2 Designing Amphiphilic Block Polymer PELA Instead of PLA 178
6.2.5.3 Effect of Preparation and Solidification Method 180
6.3 Natural Polymer (Polysaccharide) Chitosan 181
6.3.1 Strategies to Improve Encapsulation Efficiency 182
6.3.1.1 Using Step-wise Crosslinking Method to Avoid Shrinkage Stage 183
6.3.1.2 Using Chitosan Derivatives as Polymer to Adjust Microsphere Structure to Avoid Drug Crosslinking and Leakage 184
6.3.1.3 Preparing Chitosan/Alginate Complex Microsphere by Two-step Solidification Method to Avoid Drug Leakage 185
6.3.1.4 Controlling Morphologies of Microspheres to Increase Drug Loading 187
6.3.2 Strategies to Maintain Bioactivity of Drugs 188
6.3.2.1 Step-wise Crosslinking Method 189
6.3.2.2 Using Chitosan Derivatives as Polymer to Protect Protein from the Crosslinking Process 189
6.3.2.3 Self-solidification System Instead of Using Chemical Crosslinker 192
6.3.2.4 Preparing Chitosan/Alginate Complex Microsphere Instead of Chemical Crosslinking of Chitosan 193
6.4 Summary 194
References 195
7 Applications of Uniform Particles for Targeted Delivery of Anticancer Drugs 201
7.1 Introduction 201
7.2 Influence of Physical and Chemical Particle Properties on Antitumor Efficacy 202
7.2.1 Size 203
7.2.2 Surface Charge 203
7.2.3 Surface Hydrophobicity 206
7.2.4 Morphology 207
7.2.5 Flexibility 210
7.3 Classical Strategies for Targeting Tumor Tissues 211
7.3.1 Ligand/Receptor-Induced Targeting 211
7.3.2 Tumor Microenvironment Sensitive Targeting 212
7.3.2.1 pH- Sensitive Drug Delivery 213
7.3.2.2 Enzyme Responsive Drug Delivery 215
7.3.2.3 Hypoxia-Targeted Drug Delivery 215
7.3.3 Externally Activated Targeting 217
7.3.3.1 Magnetism-Based Tumor Targeting 217
7.3.3.2 Photosensitive Tumor Targeting 219
7.3.3.3 Thermal-Responsive Targeting 220
7.3.3.4 Ultrasonic-Induced Targeting 221
7.4 Novel Biomimetic Delivery Strategies 222
7.5 Summary 224
References 225
8 Applications of Uniform Particles in Vaccine Formulations 231
8.1 Introduction 231
8.2 Adjuvant and Delivery System: Assembling the Vaccine Components 232
8.2.1 Particulate Vaccine Platforms 233
8.2.1.1 Polymeric Particles 233
8.2.1.2 Polysaccharide Particles 234
8.2.1.3 Inorganic Particles 235
8.2.1.4 Liposome 236
8.2.1.5 Lipid Nanoparticle 236
8.2.2 Modularizing Strategies for Vaccine Delivery System 237
8.2.2.1 Encapsulation 237
8.2.2.2 Adsorption 238
8.2.2.3 Conjugation 239
8.3 Physicochemical Traits for the Enhanced Vaccination 240
8.3.1 Size 240
8.3.2 Charge 241
8.3.3 Shape 243
8.3.4 Hydrophobicity 245
8.3.5 Softness 246
8.4 Connecting the Dots: Strengthening on the Multi-Scale Delivery of Vaccines 248
8.4.1 Distribution 249
8.4.2 Internalization 252
8.4.3 Presentation 254
8.5 Summary 257
References 257
9 Applications of Uniform Microspheres and Super-porous Microspheres in Biochemical Engineering 267
9.1 Introductions 267
9.2 Uniform Microspheres for Chromatographic Media 268
9.2.1 Significance of Particle Size Uniformity in Chromatography 268
9.2.2 Agarose Microspheres 270
9.2.3 Konjac Glucomannan Microspheres 276
9.2.4 PST Microspheres 280
9.2.5 PGMA Microspheres 290
9.2.6 PHEMA Microspheres 292
9.2.7 Silica Microspheres 293
9.3 Super-Porous Microspheres for Vaccine Separation 297
9.3.1 Significance of Super-Porous Microspheres for Vaccine Separation 297
9.3.2 Preparation Methods for Super-Porous Microspheres 297
9.3.2.1 Super-Porous P(ST-DVB) Microspheres 299
9.3.2.2 Super-Porous P(GMA-DVB) Microspheres 299
9.3.2.3 Super-Porous Agarose Microspheres 300
9.3.2.4 Application of Membrane Emulsification Technology in the Preparation of Super-Porous Polymeric Microspheres 301
9.3.3 Surface Hydrophilization and Chemical Derivatization of Polymeric Microspheres 304
9.3.3.1 Physical Adsorption of Modified Agarose on Super-Porous P(ST-DVB) Microspheres 304
9.3.3.2 Chemical Modification with Poly(Vinyl Alcohol) of Super-Porous P(ST-DVB) Microspheres 304
9.3.3.3 Surface Hydrophilization of Super-Porous PGMA Microspheres 305
9.3.4 Applications in Biomolecules Separation 306
9.3.4.1 Excellent Flow Hydrodynamics 306
9.3.4.2 Application in Virus-Like Particles (VLPs) Separation 308
9.4 Uniform Microspheres for Cell Culture 312
9.5 Summary 316
References 317
10 Membrane Emulsification Equipment and Industrialization 323
10.1 Introduction 323
10.2 Cross-flow Membrane Emulsification Equipment 324
10.3 Premix Membrane Emulsification Equipment 326
10.4 Rotary Membrane Emulsification Equipment 329
10.5 Industrialization - Case Report 331
10.6 Summary 333
References 333
Index 335
