Guanghui Ma is Professor and Director of State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences (CAS). Having obtained her Ph.D degree from Tokyo Institute of Technology, Japan, she started her academic career at Tokyo University of Agriculture and Technology as Assistant Professor (1994). She moved to Institute of Process Engineering, CAS as a Full Professor in 2001. She was selected as an academician of CAS in 2021. Her awards include Outstanding Contribution Award from Federation of Biotechnology (AFOB) and the Second-class prize of National Invention Award.

• Preface xv1 Membrane Emulsification Process: Principle and Model 11.1 Introduction 11.2 Cross-Flow Membrane Emulsification 21.2.1 Mechanism of Droplet Formation 21.2.2 Force Balance Model 61.2.3 Torque Balance Model 81.2.3.1 Associating the Dispersed-Phase Parameters 91.2.3.2 Associating the Continuous Phase Parameters 101.2.3.3 Torque Balance Model Associating Operation Parameters 101.2.3.4 Evaluation of Controlling Factors on Droplets Uniformity by Torque Balance Model 111.2.4 Computational Fluid Dynamics 161.2.5 Models by Surface Evolver Tool 191.2.6 Models by Lattice Boltzmann Method 201.3 Premix Membrane Emulsification 211.4 Summary 23References 232 Preparation of Hydrophobic Microspheres From O/W Emulsion 272.1 Introduction 272.2 Preparation from Monomer System 282.2.1 PST–DVB Microspheres 282.2.2 PST-DMAEMA Microspheres 292.2.3 PGMA Microspheres 312.2.4 PST-HEMA Microspheres 322.2.5 PMMA Microspheres 342.3 Preparation from Performed Polymer System 372.3.1 PST–PMMA Microspheres 372.3.2 Polyurethane Urea Microspheres 392.3.3 Polyimide Prepolymer (PIP) Microspheres 402.3.4 Biodegradable Poly(Lactide) Microspheres 412.3.5 Microcapsules Containing Inorganic Materials 432.3.6 Pickering Emulsion 432.4 Morphology Control of Microspheres 452.4.1 Effect of Crosslinker on Morphology of Microspheres 452.4.2 Effect of Inert Diluents on Morphology of Microspheres 462.4.2.1 Nonsolvating Diluent Effects on Microsphere Morphology 472.4.2.2 Solvating Diluent Effects on Microsphere Morphology 492.4.3 Effect of Emulsifier/Stabilizer on Morphology of Microspheres 522.4.4 Effect of Cosurfactant on Morphology of Composite Microspheres 522.5 Summary 56References 573 Preparation of Hydrophilic Polymer Microspheres from W/O Emulsion 613.1 Introduction 613.2 Membrane Modification and Preparation 623.2.1 Hydrophobic Modification of the Membrane 623.2.2 Preparation of Hydrophobic Membrane 673.3 Preparation Microparticles from Monomer System 733.3.1 Preparation of Poly(N-isopropylacrylamide) (PNIPAM) Microspheres and Microcapsules 733.4 Preparation Microparticles from Preformed Polymer System 773.4.1 Chitosan Microspheres 773.4.2 Agarose Microspheres 833.4.3 Alginate Microspheres 893.4.4 Cellulose Microspheres 933.4.5 Glucomannan Microspheres 943.5 Other Hydrophilic Microspheres Prepared by Membrane Emulsification 953.5.1 PVA Microspheres 953.5.2 Protein Microspheres 983.6 Summary 99References 1004 Preparation of Uniform Microcapsules and Microspheres from W/O/W Double Emulsion 1054.1 Introduction 1054.2 Preparation of Uniform Microcapsules 1074.2.1 Oil-Soluble Emulsifier on the Size Distribution of Microcapsules 1094.2.2 PVA Concentration in the Outer Aqueous Phase 1104.2.3 Transmembrane Pressure on the Size Distribution of Microcapsules 1104.2.4 The Membrane with Different Pore Size 1124.2.5 Microcapsules for Drug Encapsulation 1134.2.5.1 Composition of Polymers 1134.2.5.2 The Inner Aqueous Phase Volume 1144.2.5.3 NaCl Concentration in Outer Aqueous Phase 1154.2.5.4 Drug-Loading Amount 1164.2.5.5 pH Value in Outer Aqueous Phase 1174.2.5.6 Microcapsules Size 1174.2.6 Microcapsules with Controllable Structure 1194.2.6.1 Polymer Concentrations in Oil Phase 1194.2.6.2 Solidification Rate of the Droplets 1194.2.6.3 Stabilizer Type 1214.2.6.4 Volume Fraction of the Inner Aqueous Phase 1214.3 Preparation of Composite Microspheres 1214.3.1 Water-Soluble Inhibitor 1234.3.2 Stabilizer in Outer Aqueous Phase 1234.3.3 Cross-Linking Agent 1244.4 Summary 126References 1265 Rapid Membrane Emulsification Process for Preparation of Small Microspheres 1295.1 Introduction 1295.2 Preparation of Hydrophobic Microspheres from O/W Emulsion 1305.2.1 Preparation of Polylactide-Based Particles from O/W Emulsion 1305.2.2 Preparation of PST Particles from O/W Emulsion 1325.2.3 Preparation of Drug-Loaded Particles from O/W Emulsion 1325.2.3.1 Preparation of Drug-Loaded Particles via Adsorption 1335.2.3.2 Preparation of Drug-Loaded Particles via Encapsulation 1335.2.3.3 Preparation of Polydopamine Microcapsules 1355.3 Preparation of Hydrophilic Microspheres from W/O Emulsion 1365.3.1 Preparation of Chitosan Particles 1365.3.1.1 Preparation of Chitosan Solid Particles 1365.3.1.2 Preparation of Chitosan gel Particles 1385.3.2 Preparation of Stimuli-Responsive PNIPAM Particles 1395.3.3 Preparation of Agarose Particles 1395.3.4 Preparation of Alginate Particles 1415.3.5 Preparation of Konjac Glucomannan Particles 1435.4 Preparation of Microcapsule from Double Emulsion 1445.4.1 Preparation of Drug/Antigen-Loaded Microcapsules via W/O/W Emulsions 1445.4.1.1 Preparation of Particles for Encapsulating Water-Soluble Antigen 1445.4.1.2 Preparation of Particles for Encapsulating Water-Soluble Drugs 1455.4.1.3 Preparation of Hollow Particles for Encapsulating Antigen/Drug 1475.4.2 Preparation of Microspheres with Unique Structure via W/O/W Emulsion 1475.4.2.1 Preparation of PLA/PLGA Microspheres with Single-Core Structure 1475.4.2.2 Preparation of PMMA/PLGA Microspheres with Gigaporous Structures 1495.4.2.3 Preparation of PLGA Microspheres with Nonspherical Structures 1515.4.3 Preparation of Microspheres via O/W/O Emulsion 1525.4.3.1 HTCC Chitosan Microspheres for Oral Administration via O/W/O 1535.4.3.2 CMCC Chitosan Microspheres for Encapsulating Water-Insoluble Drugs 1545.4.3.3 Chitosan Microspheres for Combined Drug Delivery and Specific Administration 1555.4.3.4 Preparation of Biomimetic Chitosan Microsphere with Cell Membrane 1575.5 Summary 158References 1586 Applications of Uniform Particles in Sustained Release of Drugs 1636.1 Introduction 1636.2 Synthetic Polymer (PLA, PLGA, and PELA) 1646.2.1 Pla 1646.2.2 Plga 1666.2.3 Pela 1676.2.4 Strategy to Improve Encapsulation Efficiency 1686.2.4.1 Effect of Additives on Encapsulation Efficiency 1686.2.4.2 Effect of pH in the External Phase 1696.2.4.3 Effect of Polymer 1706.2.4.4 Effect of Solidification Technique 1716.2.4.5 Using Post-loading Mode Instead of Pre-loading Mode 1746.2.5 Strategy to Maintain Bioactivity of Drugs 1756.2.5.1 Adding Additives to Prevent Proteins from Denaturation 1756.2.5.2 Designing Amphiphilic Block Polymer PELA Instead of PLA 1786.2.5.3 Effect of Preparation and Solidification Method 1806.3 Natural Polymer (Polysaccharide) Chitosan 1816.3.1 Strategies to Improve Encapsulation Efficiency 1826.3.1.1 Using Step-wise Crosslinking Method to Avoid Shrinkage Stage 1836.3.1.2 Using Chitosan Derivatives as Polymer to Adjust Microsphere Structure to Avoid Drug Crosslinking and Leakage 1846.3.1.3 Preparing Chitosan/Alginate Complex Microsphere by Two-step Solidification Method to Avoid Drug Leakage 1856.3.1.4 Controlling Morphologies of Microspheres to Increase Drug Loading 1876.3.2 Strategies to Maintain Bioactivity of Drugs 1886.3.2.1 Step-wise Crosslinking Method 1896.3.2.2 Using Chitosan Derivatives as Polymer to Protect Protein from the Crosslinking Process 1896.3.2.3 Self-solidification System Instead of Using Chemical Crosslinker 1926.3.2.4 Preparing Chitosan/Alginate Complex Microsphere Instead of Chemical Crosslinking of Chitosan 1936.4 Summary 194References 1957 Applications of Uniform Particles for Targeted Delivery of Anticancer Drugs 2017.1 Introduction 2017.2 Influence of Physical and Chemical Particle Properties on Antitumor Efficacy 2027.2.1 Size 2037.2.2 Surface Charge 2037.2.3 Surface Hydrophobicity 2067.2.4 Morphology 2077.2.5 Flexibility 2107.3 Classical Strategies for Targeting Tumor Tissues 2117.3.1 Ligand/Receptor-Induced Targeting 2117.3.2 Tumor Microenvironment Sensitive Targeting 2127.3.2.1 pH- Sensitive Drug Delivery 2137.3.2.2 Enzyme Responsive Drug Delivery 2157.3.2.3 Hypoxia-Targeted Drug Delivery 2157.3.3 Externally Activated Targeting 2177.3.3.1 Magnetism-Based Tumor Targeting 2177.3.3.2 Photosensitive Tumor Targeting 2197.3.3.3 Thermal-Responsive Targeting 2207.3.3.4 Ultrasonic-Induced Targeting 2217.4 Novel Biomimetic Delivery Strategies 2227.5 Summary 224References 2258 Applications of Uniform Particles in Vaccine Formulations 2318.1 Introduction 2318.2 Adjuvant and Delivery System: Assembling the Vaccine Components 2328.2.1 Particulate Vaccine Platforms 2338.2.1.1 Polymeric Particles 2338.2.1.2 Polysaccharide Particles 2348.2.1.3 Inorganic Particles 2358.2.1.4 Liposome 2368.2.1.5 Lipid Nanoparticle 2368.2.2 Modularizing Strategies for Vaccine Delivery System 2378.2.2.1 Encapsulation 2378.2.2.2 Adsorption 2388.2.2.3 Conjugation 2398.3 Physicochemical Traits for the Enhanced Vaccination 2408.3.1 Size 2408.3.2 Charge 2418.3.3 Shape 2438.3.4 Hydrophobicity 2458.3.5 Softness 2468.4 Connecting the Dots: Strengthening on the Multi-Scale Delivery of Vaccines 2488.4.1 Distribution 2498.4.2 Internalization 2528.4.3 Presentation 2548.5 Summary 257References 2579 Applications of Uniform Microspheres and Super-porous Microspheres in Biochemical Engineering 2679.1 Introductions 2679.2 Uniform Microspheres for Chromatographic Media 2689.2.1 Significance of Particle Size Uniformity in Chromatography 2689.2.2 Agarose Microspheres 2709.2.3 Konjac Glucomannan Microspheres 2769.2.4 PST Microspheres 2809.2.5 PGMA Microspheres 2909.2.6 PHEMA Microspheres 2929.2.7 Silica Microspheres 2939.3 Super-Porous Microspheres for Vaccine Separation 2979.3.1 Significance of Super-Porous Microspheres for Vaccine Separation 2979.3.2 Preparation Methods for Super-Porous Microspheres 2979.3.2.1 Super-Porous P(ST–DVB) Microspheres 2999.3.2.2 Super-Porous P(GMA–DVB) Microspheres 2999.3.2.3 Super-Porous Agarose Microspheres 3009.3.2.4 Application of Membrane Emulsification Technology in the Preparation of Super-Porous Polymeric Microspheres 3019.3.3 Surface Hydrophilization and Chemical Derivatization of Polymeric Microspheres 3049.3.3.1 Physical Adsorption of Modified Agarose on Super-Porous P(ST-DVB) Microspheres 3049.3.3.2 Chemical Modification with Poly(Vinyl Alcohol) of Super-Porous P(ST-DVB) Microspheres 3049.3.3.3 Surface Hydrophilization of Super-Porous PGMA Microspheres 3059.3.4 Applications in Biomolecules Separation 3069.3.4.1 Excellent Flow Hydrodynamics 3069.3.4.2 Application in Virus-Like Particles (VLPs) Separation 3089.4 Uniform Microspheres for Cell Culture 3129.5 Summary 316References 31710 Membrane Emulsification Equipment and Industrialization 32310.1 Introduction 32310.2 Cross-flow Membrane Emulsification Equipment 32410.3 Premix Membrane Emulsification Equipment 32610.4 Rotary Membrane Emulsification Equipment 32910.5 Industrialization – Case Report 33110.6 Summary 333References 333Index 335

Guanghui Ma is Professor and Director of State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences (CAS). Having obtained her Ph.D degree from Tokyo Institute of Technology, Japan, she started her academic career at Tokyo University of Agriculture and Technology as Assistant Professor (1994). She moved to Institute of Process Engineering, CAS as a Full Professor in 2001. She was selected as an academician of CAS in 2021. Her awards include Outstanding Contribution Award from Federation of Biotechnology (AFOB) and the Second-class prize of National Invention Award.

• Preface xv1 Membrane Emulsification Process: Principle and Model 11.1 Introduction 11.2 Cross-Flow Membrane Emulsification 21.2.1 Mechanism of Droplet Formation 21.2.2 Force Balance Model 61.2.3 Torque Balance Model 81.2.3.1 Associating the Dispersed-Phase Parameters 91.2.3.2 Associating the Continuous Phase Parameters 101.2.3.3 Torque Balance Model Associating Operation Parameters 101.2.3.4 Evaluation of Controlling Factors on Droplets Uniformity by Torque Balance Model 111.2.4 Computational Fluid Dynamics 161.2.5 Models by Surface Evolver Tool 191.2.6 Models by Lattice Boltzmann Method 201.3 Premix Membrane Emulsification 211.4 Summary 23References 232 Preparation of Hydrophobic Microspheres From O/W Emulsion 272.1 Introduction 272.2 Preparation from Monomer System 282.2.1 PST–DVB Microspheres 282.2.2 PST-DMAEMA Microspheres 292.2.3 PGMA Microspheres 312.2.4 PST-HEMA Microspheres 322.2.5 PMMA Microspheres 342.3 Preparation from Performed Polymer System 372.3.1 PST–PMMA Microspheres 372.3.2 Polyurethane Urea Microspheres 392.3.3 Polyimide Prepolymer (PIP) Microspheres 402.3.4 Biodegradable Poly(Lactide) Microspheres 412.3.5 Microcapsules Containing Inorganic Materials 432.3.6 Pickering Emulsion 432.4 Morphology Control of Microspheres 452.4.1 Effect of Crosslinker on Morphology of Microspheres 452.4.2 Effect of Inert Diluents on Morphology of Microspheres 462.4.2.1 Nonsolvating Diluent Effects on Microsphere Morphology 472.4.2.2 Solvating Diluent Effects on Microsphere Morphology 492.4.3 Effect of Emulsifier/Stabilizer on Morphology of Microspheres 522.4.4 Effect of Cosurfactant on Morphology of Composite Microspheres 522.5 Summary 56References 573 Preparation of Hydrophilic Polymer Microspheres from W/O Emulsion 613.1 Introduction 613.2 Membrane Modification and Preparation 623.2.1 Hydrophobic Modification of the Membrane 623.2.2 Preparation of Hydrophobic Membrane 673.3 Preparation Microparticles from Monomer System 733.3.1 Preparation of Poly(N-isopropylacrylamide) (PNIPAM) Microspheres and Microcapsules 733.4 Preparation Microparticles from Preformed Polymer System 773.4.1 Chitosan Microspheres 773.4.2 Agarose Microspheres 833.4.3 Alginate Microspheres 893.4.4 Cellulose Microspheres 933.4.5 Glucomannan Microspheres 943.5 Other Hydrophilic Microspheres Prepared by Membrane Emulsification 953.5.1 PVA Microspheres 953.5.2 Protein Microspheres 983.6 Summary 99References 1004 Preparation of Uniform Microcapsules and Microspheres from W/O/W Double Emulsion 1054.1 Introduction 1054.2 Preparation of Uniform Microcapsules 1074.2.1 Oil-Soluble Emulsifier on the Size Distribution of Microcapsules 1094.2.2 PVA Concentration in the Outer Aqueous Phase 1104.2.3 Transmembrane Pressure on the Size Distribution of Microcapsules 1104.2.4 The Membrane with Different Pore Size 1124.2.5 Microcapsules for Drug Encapsulation 1134.2.5.1 Composition of Polymers 1134.2.5.2 The Inner Aqueous Phase Volume 1144.2.5.3 NaCl Concentration in Outer Aqueous Phase 1154.2.5.4 Drug-Loading Amount 1164.2.5.5 pH Value in Outer Aqueous Phase 1174.2.5.6 Microcapsules Size 1174.2.6 Microcapsules with Controllable Structure 1194.2.6.1 Polymer Concentrations in Oil Phase 1194.2.6.2 Solidification Rate of the Droplets 1194.2.6.3 Stabilizer Type 1214.2.6.4 Volume Fraction of the Inner Aqueous Phase 1214.3 Preparation of Composite Microspheres 1214.3.1 Water-Soluble Inhibitor 1234.3.2 Stabilizer in Outer Aqueous Phase 1234.3.3 Cross-Linking Agent 1244.4 Summary 126References 1265 Rapid Membrane Emulsification Process for Preparation of Small Microspheres 1295.1 Introduction 1295.2 Preparation of Hydrophobic Microspheres from O/W Emulsion 1305.2.1 Preparation of Polylactide-Based Particles from O/W Emulsion 1305.2.2 Preparation of PST Particles from O/W Emulsion 1325.2.3 Preparation of Drug-Loaded Particles from O/W Emulsion 1325.2.3.1 Preparation of Drug-Loaded Particles via Adsorption 1335.2.3.2 Preparation of Drug-Loaded Particles via Encapsulation 1335.2.3.3 Preparation of Polydopamine Microcapsules 1355.3 Preparation of Hydrophilic Microspheres from W/O Emulsion 1365.3.1 Preparation of Chitosan Particles 1365.3.1.1 Preparation of Chitosan Solid Particles 1365.3.1.2 Preparation of Chitosan gel Particles 1385.3.2 Preparation of Stimuli-Responsive PNIPAM Particles 1395.3.3 Preparation of Agarose Particles 1395.3.4 Preparation of Alginate Particles 1415.3.5 Preparation of Konjac Glucomannan Particles 1435.4 Preparation of Microcapsule from Double Emulsion 1445.4.1 Preparation of Drug/Antigen-Loaded Microcapsules via W/O/W Emulsions 1445.4.1.1 Preparation of Particles for Encapsulating Water-Soluble Antigen 1445.4.1.2 Preparation of Particles for Encapsulating Water-Soluble Drugs 1455.4.1.3 Preparation of Hollow Particles for Encapsulating Antigen/Drug 1475.4.2 Preparation of Microspheres with Unique Structure via W/O/W Emulsion 1475.4.2.1 Preparation of PLA/PLGA Microspheres with Single-Core Structure 1475.4.2.2 Preparation of PMMA/PLGA Microspheres with Gigaporous Structures 1495.4.2.3 Preparation of PLGA Microspheres with Nonspherical Structures 1515.4.3 Preparation of Microspheres via O/W/O Emulsion 1525.4.3.1 HTCC Chitosan Microspheres for Oral Administration via O/W/O 1535.4.3.2 CMCC Chitosan Microspheres for Encapsulating Water-Insoluble Drugs 1545.4.3.3 Chitosan Microspheres for Combined Drug Delivery and Specific Administration 1555.4.3.4 Preparation of Biomimetic Chitosan Microsphere with Cell Membrane 1575.5 Summary 158References 1586 Applications of Uniform Particles in Sustained Release of Drugs 1636.1 Introduction 1636.2 Synthetic Polymer (PLA, PLGA, and PELA) 1646.2.1 Pla 1646.2.2 Plga 1666.2.3 Pela 1676.2.4 Strategy to Improve Encapsulation Efficiency 1686.2.4.1 Effect of Additives on Encapsulation Efficiency 1686.2.4.2 Effect of pH in the External Phase 1696.2.4.3 Effect of Polymer 1706.2.4.4 Effect of Solidification Technique 1716.2.4.5 Using Post-loading Mode Instead of Pre-loading Mode 1746.2.5 Strategy to Maintain Bioactivity of Drugs 1756.2.5.1 Adding Additives to Prevent Proteins from Denaturation 1756.2.5.2 Designing Amphiphilic Block Polymer PELA Instead of PLA 1786.2.5.3 Effect of Preparation and Solidification Method 1806.3 Natural Polymer (Polysaccharide) Chitosan 1816.3.1 Strategies to Improve Encapsulation Efficiency 1826.3.1.1 Using Step-wise Crosslinking Method to Avoid Shrinkage Stage 1836.3.1.2 Using Chitosan Derivatives as Polymer to Adjust Microsphere Structure to Avoid Drug Crosslinking and Leakage 1846.3.1.3 Preparing Chitosan/Alginate Complex Microsphere by Two-step Solidification Method to Avoid Drug Leakage 1856.3.1.4 Controlling Morphologies of Microspheres to Increase Drug Loading 1876.3.2 Strategies to Maintain Bioactivity of Drugs 1886.3.2.1 Step-wise Crosslinking Method 1896.3.2.2 Using Chitosan Derivatives as Polymer to Protect Protein from the Crosslinking Process 1896.3.2.3 Self-solidification System Instead of Using Chemical Crosslinker 1926.3.2.4 Preparing Chitosan/Alginate Complex Microsphere Instead of Chemical Crosslinking of Chitosan 1936.4 Summary 194References 1957 Applications of Uniform Particles for Targeted Delivery of Anticancer Drugs 2017.1 Introduction 2017.2 Influence of Physical and Chemical Particle Properties on Antitumor Efficacy 2027.2.1 Size 2037.2.2 Surface Charge 2037.2.3 Surface Hydrophobicity 2067.2.4 Morphology 2077.2.5 Flexibility 2107.3 Classical Strategies for Targeting Tumor Tissues 2117.3.1 Ligand/Receptor-Induced Targeting 2117.3.2 Tumor Microenvironment Sensitive Targeting 2127.3.2.1 pH- Sensitive Drug Delivery 2137.3.2.2 Enzyme Responsive Drug Delivery 2157.3.2.3 Hypoxia-Targeted Drug Delivery 2157.3.3 Externally Activated Targeting 2177.3.3.1 Magnetism-Based Tumor Targeting 2177.3.3.2 Photosensitive Tumor Targeting 2197.3.3.3 Thermal-Responsive Targeting 2207.3.3.4 Ultrasonic-Induced Targeting 2217.4 Novel Biomimetic Delivery Strategies 2227.5 Summary 224References 2258 Applications of Uniform Particles in Vaccine Formulations 2318.1 Introduction 2318.2 Adjuvant and Delivery System: Assembling the Vaccine Components 2328.2.1 Particulate Vaccine Platforms 2338.2.1.1 Polymeric Particles 2338.2.1.2 Polysaccharide Particles 2348.2.1.3 Inorganic Particles 2358.2.1.4 Liposome 2368.2.1.5 Lipid Nanoparticle 2368.2.2 Modularizing Strategies for Vaccine Delivery System 2378.2.2.1 Encapsulation 2378.2.2.2 Adsorption 2388.2.2.3 Conjugation 2398.3 Physicochemical Traits for the Enhanced Vaccination 2408.3.1 Size 2408.3.2 Charge 2418.3.3 Shape 2438.3.4 Hydrophobicity 2458.3.5 Softness 2468.4 Connecting the Dots: Strengthening on the Multi-Scale Delivery of Vaccines 2488.4.1 Distribution 2498.4.2 Internalization 2528.4.3 Presentation 2548.5 Summary 257References 2579 Applications of Uniform Microspheres and Super-porous Microspheres in Biochemical Engineering 2679.1 Introductions 2679.2 Uniform Microspheres for Chromatographic Media 2689.2.1 Significance of Particle Size Uniformity in Chromatography 2689.2.2 Agarose Microspheres 2709.2.3 Konjac Glucomannan Microspheres 2769.2.4 PST Microspheres 2809.2.5 PGMA Microspheres 2909.2.6 PHEMA Microspheres 2929.2.7 Silica Microspheres 2939.3 Super-Porous Microspheres for Vaccine Separation 2979.3.1 Significance of Super-Porous Microspheres for Vaccine Separation 2979.3.2 Preparation Methods for Super-Porous Microspheres 2979.3.2.1 Super-Porous P(ST–DVB) Microspheres 2999.3.2.2 Super-Porous P(GMA–DVB) Microspheres 2999.3.2.3 Super-Porous Agarose Microspheres 3009.3.2.4 Application of Membrane Emulsification Technology in the Preparation of Super-Porous Polymeric Microspheres 3019.3.3 Surface Hydrophilization and Chemical Derivatization of Polymeric Microspheres 3049.3.3.1 Physical Adsorption of Modified Agarose on Super-Porous P(ST-DVB) Microspheres 3049.3.3.2 Chemical Modification with Poly(Vinyl Alcohol) of Super-Porous P(ST-DVB) Microspheres 3049.3.3.3 Surface Hydrophilization of Super-Porous PGMA Microspheres 3059.3.4 Applications in Biomolecules Separation 3069.3.4.1 Excellent Flow Hydrodynamics 3069.3.4.2 Application in Virus-Like Particles (VLPs) Separation 3089.4 Uniform Microspheres for Cell Culture 3129.5 Summary 316References 31710 Membrane Emulsification Equipment and Industrialization 32310.1 Introduction 32310.2 Cross-flow Membrane Emulsification Equipment 32410.3 Premix Membrane Emulsification Equipment 32610.4 Rotary Membrane Emulsification Equipment 32910.5 Industrialization – Case Report 33110.6 Summary 333References 333Index 335

Guanghui Ma is Professor and Director of State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences (CAS). Having obtained her Ph.D degree from Tokyo Institute of Technology, Japan, she started her academic career at Tokyo University of Agriculture and Technology as Assistant Professor (1994). She moved to Institute of Process Engineering, CAS as a Full Professor in 2001. She was selected as an academician of CAS in 2021. Her awards include Outstanding Contribution Award from Federation of Biotechnology (AFOB) and the Second-class prize of National Invention Award.

• Preface xv1 Membrane Emulsification Process: Principle and Model 11.1 Introduction 11.2 Cross-Flow Membrane Emulsification 21.2.1 Mechanism of Droplet Formation 21.2.2 Force Balance Model 61.2.3 Torque Balance Model 81.2.3.1 Associating the Dispersed-Phase Parameters 91.2.3.2 Associating the Continuous Phase Parameters 101.2.3.3 Torque Balance Model Associating Operation Parameters 101.2.3.4 Evaluation of Controlling Factors on Droplets Uniformity by Torque Balance Model 111.2.4 Computational Fluid Dynamics 161.2.5 Models by Surface Evolver Tool 191.2.6 Models by Lattice Boltzmann Method 201.3 Premix Membrane Emulsification 211.4 Summary 23References 232 Preparation of Hydrophobic Microspheres From O/W Emulsion 272.1 Introduction 272.2 Preparation from Monomer System 282.2.1 PST–DVB Microspheres 282.2.2 PST-DMAEMA Microspheres 292.2.3 PGMA Microspheres 312.2.4 PST-HEMA Microspheres 322.2.5 PMMA Microspheres 342.3 Preparation from Performed Polymer System 372.3.1 PST–PMMA Microspheres 372.3.2 Polyurethane Urea Microspheres 392.3.3 Polyimide Prepolymer (PIP) Microspheres 402.3.4 Biodegradable Poly(Lactide) Microspheres 412.3.5 Microcapsules Containing Inorganic Materials 432.3.6 Pickering Emulsion 432.4 Morphology Control of Microspheres 452.4.1 Effect of Crosslinker on Morphology of Microspheres 452.4.2 Effect of Inert Diluents on Morphology of Microspheres 462.4.2.1 Nonsolvating Diluent Effects on Microsphere Morphology 472.4.2.2 Solvating Diluent Effects on Microsphere Morphology 492.4.3 Effect of Emulsifier/Stabilizer on Morphology of Microspheres 522.4.4 Effect of Cosurfactant on Morphology of Composite Microspheres 522.5 Summary 56References 573 Preparation of Hydrophilic Polymer Microspheres from W/O Emulsion 613.1 Introduction 613.2 Membrane Modification and Preparation 623.2.1 Hydrophobic Modification of the Membrane 623.2.2 Preparation of Hydrophobic Membrane 673.3 Preparation Microparticles from Monomer System 733.3.1 Preparation of Poly(N-isopropylacrylamide) (PNIPAM) Microspheres and Microcapsules 733.4 Preparation Microparticles from Preformed Polymer System 773.4.1 Chitosan Microspheres 773.4.2 Agarose Microspheres 833.4.3 Alginate Microspheres 893.4.4 Cellulose Microspheres 933.4.5 Glucomannan Microspheres 943.5 Other Hydrophilic Microspheres Prepared by Membrane Emulsification 953.5.1 PVA Microspheres 953.5.2 Protein Microspheres 983.6 Summary 99References 1004 Preparation of Uniform Microcapsules and Microspheres from W/O/W Double Emulsion 1054.1 Introduction 1054.2 Preparation of Uniform Microcapsules 1074.2.1 Oil-Soluble Emulsifier on the Size Distribution of Microcapsules 1094.2.2 PVA Concentration in the Outer Aqueous Phase 1104.2.3 Transmembrane Pressure on the Size Distribution of Microcapsules 1104.2.4 The Membrane with Different Pore Size 1124.2.5 Microcapsules for Drug Encapsulation 1134.2.5.1 Composition of Polymers 1134.2.5.2 The Inner Aqueous Phase Volume 1144.2.5.3 NaCl Concentration in Outer Aqueous Phase 1154.2.5.4 Drug-Loading Amount 1164.2.5.5 pH Value in Outer Aqueous Phase 1174.2.5.6 Microcapsules Size 1174.2.6 Microcapsules with Controllable Structure 1194.2.6.1 Polymer Concentrations in Oil Phase 1194.2.6.2 Solidification Rate of the Droplets 1194.2.6.3 Stabilizer Type 1214.2.6.4 Volume Fraction of the Inner Aqueous Phase 1214.3 Preparation of Composite Microspheres 1214.3.1 Water-Soluble Inhibitor 1234.3.2 Stabilizer in Outer Aqueous Phase 1234.3.3 Cross-Linking Agent 1244.4 Summary 126References 1265 Rapid Membrane Emulsification Process for Preparation of Small Microspheres 1295.1 Introduction 1295.2 Preparation of Hydrophobic Microspheres from O/W Emulsion 1305.2.1 Preparation of Polylactide-Based Particles from O/W Emulsion 1305.2.2 Preparation of PST Particles from O/W Emulsion 1325.2.3 Preparation of Drug-Loaded Particles from O/W Emulsion 1325.2.3.1 Preparation of Drug-Loaded Particles via Adsorption 1335.2.3.2 Preparation of Drug-Loaded Particles via Encapsulation 1335.2.3.3 Preparation of Polydopamine Microcapsules 1355.3 Preparation of Hydrophilic Microspheres from W/O Emulsion 1365.3.1 Preparation of Chitosan Particles 1365.3.1.1 Preparation of Chitosan Solid Particles 1365.3.1.2 Preparation of Chitosan gel Particles 1385.3.2 Preparation of Stimuli-Responsive PNIPAM Particles 1395.3.3 Preparation of Agarose Particles 1395.3.4 Preparation of Alginate Particles 1415.3.5 Preparation of Konjac Glucomannan Particles 1435.4 Preparation of Microcapsule from Double Emulsion 1445.4.1 Preparation of Drug/Antigen-Loaded Microcapsules via W/O/W Emulsions 1445.4.1.1 Preparation of Particles for Encapsulating Water-Soluble Antigen 1445.4.1.2 Preparation of Particles for Encapsulating Water-Soluble Drugs 1455.4.1.3 Preparation of Hollow Particles for Encapsulating Antigen/Drug 1475.4.2 Preparation of Microspheres with Unique Structure via W/O/W Emulsion 1475.4.2.1 Preparation of PLA/PLGA Microspheres with Single-Core Structure 1475.4.2.2 Preparation of PMMA/PLGA Microspheres with Gigaporous Structures 1495.4.2.3 Preparation of PLGA Microspheres with Nonspherical Structures 1515.4.3 Preparation of Microspheres via O/W/O Emulsion 1525.4.3.1 HTCC Chitosan Microspheres for Oral Administration via O/W/O 1535.4.3.2 CMCC Chitosan Microspheres for Encapsulating Water-Insoluble Drugs 1545.4.3.3 Chitosan Microspheres for Combined Drug Delivery and Specific Administration 1555.4.3.4 Preparation of Biomimetic Chitosan Microsphere with Cell Membrane 1575.5 Summary 158References 1586 Applications of Uniform Particles in Sustained Release of Drugs 1636.1 Introduction 1636.2 Synthetic Polymer (PLA, PLGA, and PELA) 1646.2.1 Pla 1646.2.2 Plga 1666.2.3 Pela 1676.2.4 Strategy to Improve Encapsulation Efficiency 1686.2.4.1 Effect of Additives on Encapsulation Efficiency 1686.2.4.2 Effect of pH in the External Phase 1696.2.4.3 Effect of Polymer 1706.2.4.4 Effect of Solidification Technique 1716.2.4.5 Using Post-loading Mode Instead of Pre-loading Mode 1746.2.5 Strategy to Maintain Bioactivity of Drugs 1756.2.5.1 Adding Additives to Prevent Proteins from Denaturation 1756.2.5.2 Designing Amphiphilic Block Polymer PELA Instead of PLA 1786.2.5.3 Effect of Preparation and Solidification Method 1806.3 Natural Polymer (Polysaccharide) Chitosan 1816.3.1 Strategies to Improve Encapsulation Efficiency 1826.3.1.1 Using Step-wise Crosslinking Method to Avoid Shrinkage Stage 1836.3.1.2 Using Chitosan Derivatives as Polymer to Adjust Microsphere Structure to Avoid Drug Crosslinking and Leakage 1846.3.1.3 Preparing Chitosan/Alginate Complex Microsphere by Two-step Solidification Method to Avoid Drug Leakage 1856.3.1.4 Controlling Morphologies of Microspheres to Increase Drug Loading 1876.3.2 Strategies to Maintain Bioactivity of Drugs 1886.3.2.1 Step-wise Crosslinking Method 1896.3.2.2 Using Chitosan Derivatives as Polymer to Protect Protein from the Crosslinking Process 1896.3.2.3 Self-solidification System Instead of Using Chemical Crosslinker 1926.3.2.4 Preparing Chitosan/Alginate Complex Microsphere Instead of Chemical Crosslinking of Chitosan 1936.4 Summary 194References 1957 Applications of Uniform Particles for Targeted Delivery of Anticancer Drugs 2017.1 Introduction 2017.2 Influence of Physical and Chemical Particle Properties on Antitumor Efficacy 2027.2.1 Size 2037.2.2 Surface Charge 2037.2.3 Surface Hydrophobicity 2067.2.4 Morphology 2077.2.5 Flexibility 2107.3 Classical Strategies for Targeting Tumor Tissues 2117.3.1 Ligand/Receptor-Induced Targeting 2117.3.2 Tumor Microenvironment Sensitive Targeting 2127.3.2.1 pH- Sensitive Drug Delivery 2137.3.2.2 Enzyme Responsive Drug Delivery 2157.3.2.3 Hypoxia-Targeted Drug Delivery 2157.3.3 Externally Activated Targeting 2177.3.3.1 Magnetism-Based Tumor Targeting 2177.3.3.2 Photosensitive Tumor Targeting 2197.3.3.3 Thermal-Responsive Targeting 2207.3.3.4 Ultrasonic-Induced Targeting 2217.4 Novel Biomimetic Delivery Strategies 2227.5 Summary 224References 2258 Applications of Uniform Particles in Vaccine Formulations 2318.1 Introduction 2318.2 Adjuvant and Delivery System: Assembling the Vaccine Components 2328.2.1 Particulate Vaccine Platforms 2338.2.1.1 Polymeric Particles 2338.2.1.2 Polysaccharide Particles 2348.2.1.3 Inorganic Particles 2358.2.1.4 Liposome 2368.2.1.5 Lipid Nanoparticle 2368.2.2 Modularizing Strategies for Vaccine Delivery System 2378.2.2.1 Encapsulation 2378.2.2.2 Adsorption 2388.2.2.3 Conjugation 2398.3 Physicochemical Traits for the Enhanced Vaccination 2408.3.1 Size 2408.3.2 Charge 2418.3.3 Shape 2438.3.4 Hydrophobicity 2458.3.5 Softness 2468.4 Connecting the Dots: Strengthening on the Multi-Scale Delivery of Vaccines 2488.4.1 Distribution 2498.4.2 Internalization 2528.4.3 Presentation 2548.5 Summary 257References 2579 Applications of Uniform Microspheres and Super-porous Microspheres in Biochemical Engineering 2679.1 Introductions 2679.2 Uniform Microspheres for Chromatographic Media 2689.2.1 Significance of Particle Size Uniformity in Chromatography 2689.2.2 Agarose Microspheres 2709.2.3 Konjac Glucomannan Microspheres 2769.2.4 PST Microspheres 2809.2.5 PGMA Microspheres 2909.2.6 PHEMA Microspheres 2929.2.7 Silica Microspheres 2939.3 Super-Porous Microspheres for Vaccine Separation 2979.3.1 Significance of Super-Porous Microspheres for Vaccine Separation 2979.3.2 Preparation Methods for Super-Porous Microspheres 2979.3.2.1 Super-Porous P(ST–DVB) Microspheres 2999.3.2.2 Super-Porous P(GMA–DVB) Microspheres 2999.3.2.3 Super-Porous Agarose Microspheres 3009.3.2.4 Application of Membrane Emulsification Technology in the Preparation of Super-Porous Polymeric Microspheres 3019.3.3 Surface Hydrophilization and Chemical Derivatization of Polymeric Microspheres 3049.3.3.1 Physical Adsorption of Modified Agarose on Super-Porous P(ST-DVB) Microspheres 3049.3.3.2 Chemical Modification with Poly(Vinyl Alcohol) of Super-Porous P(ST-DVB) Microspheres 3049.3.3.3 Surface Hydrophilization of Super-Porous PGMA Microspheres 3059.3.4 Applications in Biomolecules Separation 3069.3.4.1 Excellent Flow Hydrodynamics 3069.3.4.2 Application in Virus-Like Particles (VLPs) Separation 3089.4 Uniform Microspheres for Cell Culture 3129.5 Summary 316References 31710 Membrane Emulsification Equipment and Industrialization 32310.1 Introduction 32310.2 Cross-flow Membrane Emulsification Equipment 32410.3 Premix Membrane Emulsification Equipment 32610.4 Rotary Membrane Emulsification Equipment 32910.5 Industrialization – Case Report 33110.6 Summary 333References 333Index 335