Nanoparticle Technology for Drug Delivery

Nanoparticles, products of nanotechnology, are of increasing interest to the pharmaceutical community. They can increase drug solubility, enhance bioavailability, allow tissue targeting, offer decreased side-effects, and improve therapeutic efficacy. Presenting the most pertinent and practical issues in the manufacturing and biological application of nanoparticles, this source presents state-of-the-art scientific contributions by seasoned authorities in the field.

Preface

iii

Contributors

xi

PART I: TECHNOLOGIES FOR NANOPARTICLE MANUFACTURING

Fundamentals of Drug Nanoparticles

1

(20)

Ram B. Gupta

Introduction

1

(1)

Nanoparticle Size

2

(1)

Nanoparticle Surface

3

(1)

Nanoparticle Suspension and Settling

4

(2)

Magnetic and Optical Properties

6

(1)

Production of Nanoparticles

6

(6)

Biological Transport of Nanoparticles

12

(5)

Conclusions

17

(1)

References

18

(3)

Manufacturing of Nanoparticles by Milling and Homogenization Techniques

21

(32)

Rainer H. Muller

Jan Moschwitzer

Faris Nadiem Bushrab

Introduction

21

(4)

Pearl/Ball-Milling Technology for the Production of Drug Nanocrystals

25

(3)

Drug Nanocrystals Produced by High-Pressure Homogenization

28

(5)

Production of Drug Nanocrystal Compounds by Spray-Drying

33

(2)

Production in Nonaqueous Liquids

35

(2)

Production in Hot-Melted Matrices

37

(4)

Pelletization Techniques

41

(4)

Direct Compress

45

(2)

References

47

(6)

Supercritical Fluid Technology for Particle Engineering

53

(32)

Ram B. Gupta

Introduction

53

(1)

Supercritical CO2

54

(1)

Solubility in Supercritical CO2

55

(4)

Rapid Expansion of Supercritical Solution for Particle Formation

59

(4)

RESS with Solid Cosolvent for Nanoparticle Formation

63

(3)

Supercritical Antisolvent Process for Particle Formation

66

(3)

SAS with Enhanced Mass (EM) Transfer (SAS-EM) Process for Nanoparticle Formation

69

(1)

Fundamentals Governing Particle Formation with RESS and SAS

70

(4)

Other Applications of SCFs for Particle Engineering

74

(4)

Safety and Health Issues

78

(1)

Conclusions

78

(1)

References

79

(6)

Polymer or Protein Stabilized Nanoparticles from Emulsions

85

(18)

Ram B. Gupta

Introduction

85

(1)

Emulsification Solvent Evaporation Process

86

(1)

Emulsification

87

(6)

Nanoparticle Hardening

93

(4)

Residual Solvent and Emulsifier

97

(1)

Protein Stabilized Nanoparticles

98

(1)

Conclusions

99

(2)

References

101

(2)

PART II: NANOPARTICLE CHARACTERIZATION AND PROPERTIES

Physical Characterization of Nanoparticles

103

(36)

Roy J. Haskell

Introduction

103

(2)

Measurement of Size

105

(4)

Available Methods

109

(10)

In Vitro Release

119

(2)

Example: Particle Size

121

(9)

Conclusions

130

(2)

References

132

(7)

Nanoparticle Interface: An Important Determinant in Nanoparticle-Mediated Drug/Gene Delivery

139

(22)

Sanjeeb K. Sahoo

Vinod Labhasetwar

Introduction

139

(1)

Influence of Emulsifier on Pharmaceutical Properties of Nanoparticles

140

(8)

Implication on Cellular Uptake/Toxicity/Gene Delivery

148

(5)

Biodistribution

153

(1)

Conclusions

154

(1)

References

154

(7)

Toxicological Characterization of Engineered Nanoparticles

161

(38)

Paul J. A. Borm

Roel P. F. Schins

Introduction

161

(3)

Inhalation of Particles

164

(6)

Effects of Nanoparticles

170

(8)

Screening Engineered NP for Toxicological Hazards

178

(9)

Conclusion

187

(1)

References

188

(11)

PART III: DRUG DELIVERY APPLICATIONS OF NANOPARTICLES

Injectable Nanoparticles for Efficient Drug Delivery

199

(32)

Barrett Rabinow

Mahesh V. Chaubal

Introduction: Medical Needs Addressable by Nanoparticulate Drug Delivery

199

(10)

Types of Carriers

209

(6)

Coating Functionality

215

(1)

External Assistance in Targeting

215

(1)

Drugs Incorporated

216

(1)

Clinical Development

217

(3)

Conclusions

220

(1)

References

221

(10)

Polymeric Nanoparticles for Oral Drug Delivery

231

(42)

Vivekanand Bhardwaj

Majeti Naga Venkata Ravi Kumar

Introduction

231

(1)

Physiology of GIT with Relevance to Particulate Uptake

232

(4)

Particle Size and Surface Charge: Critical Factors in Particle Absorption

236

(1)

Bioadhesion

237

(4)

Tracer Techniques

241

(2)

In Vitro and In Vivo Models

243

(1)

Nanoparticle Formulation

244

(9)

Applications

253

(7)

Future Directions

260

(2)

References

262

(11)

Brain Delivery by Nanoparticles

273

(46)

Svetlana Gelperina

Introduction

273

(3)

Biodistribution Studies

276

(13)

Pharmacological Activity

289

(7)

Mechanisms of Drug Delivery to the Brain by Means of Polymeric NP

296

(13)

Conclusions

309

(2)

References

311

(8)

Nanoparticles for Ocular Drug Delivery

319

(42)

Aniruddha C. Amrite

Uday B. Kompella

Introduction

319

(3)

Disposition of Nanoparticles in the Eye

322

(14)

Ocular Drug Delivery Enhancement Using Nanoparticles

336

(11)

Safety and Tolerability of Particulate Systems

347

(5)

Conclusions

352

(1)

References

353

(8)

DNA Nanoparticle Gene Delivery Systems

361

(20)

Moses O. Oyewumi

Kevin G. Rice

Gene Delivery Vectors

361

(2)

Polymers Used to Prepare DNA Nanoparticles

363

(2)

Physical Properties of DNA Nanoparticles

365

(6)

Biodistribution and Trafficking of DNA Nanoparticles

371

(1)

Conclusions

372

(1)

References

373

(8)

PART IV: CLINICAL, ETHICAL, AND REGULATORY ISSUES

Nanotechnology and Nanoparticles: Clinical, Ethical, and Regulatory Issues

381

(16)

Makena Hammond

Uday B. Kompella

Introduction

381

(1)

Clinical Aspects

382

(3)

Environmental, Social, and Ethical Issues

385

(3)

Regulatory Challenges

388

(4)

Conclusions

392

(1)

References

393

(4)

Index

397

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Nanoparticle Technology for Drug Delivery

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Table of Contents

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