Nanoparticulate Drug Delivery Systems DRUGS AND THE PHARMACEUTICAL SCIENCES A Series of Textbooks and Monographs Executive Editor James Swarbrick PharmaceuTech, Inc Pinehurst, North Carolina Advisory Board Larry L Augsburger Harry G Brittain University of Maryland Baltimore, Maryland Center for Pharmaceutical Physics Milford, New Jersey Jennifer B Dressman Johann Wolfgang Goethe University Frankfurt, Germany Anthony J Hickey University of North Carolina School of Pharmacy Chapel Hill, North Carolina Jeffrey A Hughes University of Florida College of Pharmacy Gainesville, Florida Trevor M Jones The Association of the British Pharmaceutical Industry London, United Kingdom Vincent H L Lee Ajaz Hussain Sandoz Princeton, New Jersey Hans E Junginger Leiden/Amsterdam Center for Drug Research Leiden, The Netherlands Stephen G Schulman University of Southern California Los Angeles, California University of Florida Gainesville, Florida Jerome P Skelly Elizabeth M Topp Alexandria, Virginia University of Kansas School of Pharmacy Lawrence, Kansas Geoffrey T Tucker University of Sheffield Royal Hallamshire Hospital Sheffield, United Kingdom Peter York University of Bradford School of Pharmacy Bradford, United Kingdom Pharmacokinetics, Milo Gibaldi and Donald Perrier Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Sidney H Willig, Murray M Tuckerman, and William S Hitchings IV Microencapsulation, edited by J R Nixon Drug Metabolism: Chemical and Biochemical Aspects, Bernard Testa and Peter Jenner New Drugs: Discovery and Development, edited by Alan A Rubin Sustained and Controlled Release Drug Delivery Systems, edited by Joseph R Robinson Modern Pharmaceutics, edited by Gilbert S Banker and Christopher T Rhodes Prescription Drugs in Short Supply: Case Histories, Michael A Schwartz Activated Charcoal: Antidotal and Other Medical Uses, David O Cooney 10 Concepts in Drug Metabolism (in two parts), edited by Peter Jenner and Bernard Testa 11 Pharmaceutical Analysis: Modern Methods (in two parts), edited by James W Munson 12 Techniques of Solubilization of Drugs, edited by Samuel H Yalkowsky 13 Orphan Drugs, edited by Fred E Karch 14 Novel Drug Delivery Systems: Fundamentals, Developmental Concepts, Biomedical Assessments, Yie W Chien 15 Pharmacokinetics: Second Edition, Revised and Expanded, Milo Gibaldi and Donald Perrier 16 Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Second Edition, Revised and Expanded, Sidney H Willig, Murray M Tuckerman, and William S Hitchings IV 17 Formulation of Veterinary Dosage Forms, edited by Jack Blodinger 18 Dermatological Formulations: Percutaneous Absorption, Brian W Barry 19 The Clinical Research Process in the Pharmaceutical Industry, edited by Gary M Matoren 20 Microencapsulation and Related Drug Processes, Patrick B Deasy 21 Drugs and Nutrients: The Interactive Effects, edited by Daphne A Roe and T Colin Campbell 22 Biotechnology of Industrial Antibiotics, Erick J Vandamme 23 Pharmaceutical Process Validation, edited by Bernard T Loftus and Robert A Nash 24 Anticancer and Interferon Agents: Synthesis and Properties, edited by Raphael M Ottenbrite and George B Butler 25 Pharmaceutical Statistics: Practical and Clinical Applications, Sanford Bolton 26 Drug Dynamics for Analytical, Clinical, and Biological Chemists, Benjamin J Gudzinowicz, Burrows T Younkin, Jr., and Michael J Gudzinowicz 27 Modern Analysis of Antibiotics, edited by Adjoran Aszalos 28 Solubility and Related Properties, Kenneth C James 29 Controlled Drug Delivery: Fundamentals and Applications, Second Edition, Revised and Expanded, edited by Joseph R Robinson and Vincent H Lee 30 New Drug Approval Process: Clinical and Regulatory Management, edited by Richard A Guarino 31 Transdermal Controlled Systemic Medications, edited by Yie W Chien 32 Drug Delivery Devices: Fundamentals and Applications, edited by Praveen Tyle 33 Pharmacokinetics: Regulatory • Industrial • Academic Perspectives, edited by Peter G Welling and Francis L S Tse 34 Clinical Drug Trials and Tribulations, edited by Allen E Cato 35 Transdermal Drug Delivery: Developmental Issues and Research Initiatives, edited by Jonathan Hadgraft and Richard H Guy 36 Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, edited by James W McGinity 37 Pharmaceutical Pelletization Technology, edited by Isaac GhebreSellassie 38 Good Laboratory Practice Regulations, edited by Allen F Hirsch 39 Nasal Systemic Drug Delivery, Yie W Chien, Kenneth S E Su, and Shyi-Feu Chang 40 Modern Pharmaceutics: Second Edition, Revised and Expanded, edited by Gilbert S Banker and Christopher T Rhodes 41 Specialized Drug Delivery Systems: Manufacturing and Production Technology, edited by Praveen Tyle 42 Topical Drug Delivery Formulations, edited by David W Osborne and Anton H Amann 43 Drug Stability: Principles and Practices, Jens T Carstensen 44 Pharmaceutical Statistics: Practical and Clinical Applications, Second Edition, Revised and Expanded, Sanford Bolton 45 Biodegradable Polymers as Drug Delivery Systems, edited by Mark Chasin and Robert Langer 46 Preclinical Drug Disposition: A Laboratory Handbook, Francis L S Tse and James J Jaffe 47 HPLC in the Pharmaceutical Industry, edited by Godwin W Fong and Stanley K Lam 48 Pharmaceutical Bioequivalence, edited by Peter G Welling, Francis L S Tse, and Shrikant V Dinghe 49 Pharmaceutical Dissolution Testing, Umesh V Banakar 50 Novel Drug Delivery Systems: Second Edition, Revised and Expanded, Yie W Chien 51 Managing the Clinical Drug Development Process, David M Cocchetto and Ronald V Nardi 52 Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Third Edition, edited by Sidney H Willig and James R Stoker 53 Prodrugs: Topical and Ocular Drug Delivery, edited by Kenneth B Sloan 54 Pharmaceutical Inhalation Aerosol Technology, edited by Anthony J Hickey 55 Radiopharmaceuticals: Chemistry and Pharmacology, edited by Adrian D Nunn 56 New Drug Approval Process: Second Edition, Revised and Expanded, edited by Richard A Guarino 57 Pharmaceutical Process Validation: Second Edition, Revised and Expanded, edited by Ira R Berry and Robert A Nash 58 Ophthalmic Drug Delivery Systems, edited by Ashim K Mitra 59 Pharmaceutical Skin Penetration Enhancement, edited by Kenneth A Walters and Jonathan Hadgraft 60 Colonic Drug Absorption and Metabolism, edited by Peter R Bieck 61 Pharmaceutical Particulate Carriers: Therapeutic Applications, edited by Alain Rolland 62 Drug Permeation Enhancement: Theory and Applications, edited by Dean S Hsieh 63 Glycopeptide Antibiotics, edited by Ramakrishnan Nagarajan 64 Achieving Sterility in Medical and Pharmaceutical Products, Nigel A Halls 65 Multiparticulate Oral Drug Delivery, edited by Isaac Ghebre-Sellassie 66 Colloidal Drug Delivery Systems, edited by Jưrg Kreuter 67 Pharmacokinetics: Regulatory • Industrial • Academic Perspectives, Second Edition, edited by Peter G Welling and Francis L S Tse 68 Drug Stability: Principles and Practices, Second Edition, Revised and Expanded, Jens T Carstensen 69 Good Laboratory Practice Regulations: Second Edition, Revised and Expanded, edited by Sandy Weinberg 70 Physical Characterization of Pharmaceutical Solids, edited by Harry G Brittain 71 Pharmaceutical Powder Compaction Technology, edited by Göran Alderborn and Christer Nyström 72 Modern Pharmaceutics: Third Edition, Revised and Expanded, edited by Gilbert S Banker and Christopher T Rhodes 73 Microencapsulation: Methods and Industrial Applications, edited by Simon Benita 74 Oral Mucosal Drug Delivery, edited by Michael J Rathbone 75 Clinical Research in Pharmaceutical Development, edited by Barry Bleidt and Michael Montagne 76 The Drug Development Process: Increasing Efficiency and Cost Effectiveness, edited by Peter G Welling, Louis Lasagna, and Umesh V Banakar 77 Microparticulate Systems for the Delivery of Proteins and Vaccines, edited by Smadar Cohen and Howard Bernstein 78 Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Fourth Edition, Revised and Expanded, Sidney H Willig and James R Stoker 79 Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms: Second Edition, Revised and Expanded, edited by James W McGinity 80 Pharmaceutical Statistics: Practical and Clinical Applications, Third Edition, Sanford Bolton 81 Handbook of Pharmaceutical Granulation Technology, edited by Dilip M Parikh 82 Biotechnology of Antibiotics: Second Edition, Revised and Expanded, edited by William R Strohl 83 Mechanisms of Transdermal Drug Delivery, edited by Russell O Potts and Richard H Guy 84 Pharmaceutical Enzymes, edited by Albert Lauwers and Simon Scharpé 85 Development of Biopharmaceutical Parenteral Dosage Forms, edited by John A Bontempo 86 Pharmaceutical Project Management, edited by Tony Kennedy 87 Drug Products for Clinical Trials: An International Guide to Formulation • Production • Quality Control, edited by Donald C Monkhouse and Christopher T Rhodes 88 Development and Formulation of Veterinary Dosage Forms: Second Edition, Revised and Expanded, edited by Gregory E Hardee and J Desmond Baggot 89 Receptor-Based Drug Design, edited by Paul Leff 90 Automation and Validation of Information in Pharmaceutical Processing, edited by Joseph F deSpautz 91 Dermal Absorption and Toxicity Assessment, edited by Michael S Roberts and Kenneth A Walters 92 Pharmaceutical Experimental Design, Gareth A Lewis, Didier Mathieu, and Roger Phan-Tan-Luu 93 Preparing for FDA Pre-Approval Inspections, edited by Martin D Hynes III 94 Pharmaceutical Excipients: Characterization by IR, Raman, and NMR Spectroscopy, David E Bugay and W Paul Findlay 95 Polymorphism in Pharmaceutical Solids, edited by Harry G Brittain 96 Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products, edited by Louis Rey and Joan C May 97 Percutaneous Absorption: Drugs–Cosmetics–Mechanisms–Methodology, Third Edition, Revised and Expanded, edited by Robert L Bronaugh and Howard I Maibach 98 Bioadhesive Drug Delivery Systems: Fundamentals, Novel Approaches, and Development, edited by Edith Mathiowitz, Donald E Chickering III, and Claus-Michael Lehr 99 Protein Formulation and Delivery, edited by Eugene J McNally 100 New Drug Approval Process: Third Edition, The Global Challenge, edited by Richard A Guarino 101 Peptide and Protein Drug Analysis, edited by Ronald E Reid 102 Transport Processes in Pharmaceutical Systems, edited by Gordon L Amidon, Ping I Lee, and Elizabeth M Topp 103 Excipient Toxicity and Safety, edited by Myra L Weiner and Lois A Kotkoskie 104 The Clinical Audit in Pharmaceutical Development, edited by Michael R Hamrell 105 Pharmaceutical Emulsions and Suspensions, edited by Francoise Nielloud and Gilberte Marti-Mestres 106 Oral Drug Absorption: Prediction and Assessment, edited by Jennifer B Dressman and Hans Lennernäs 107 Drug Stability: Principles and Practices, Third Edition, Revised and Expanded, edited by Jens T Carstensen and C T Rhodes 108 Containment in the Pharmaceutical Industry, edited by James P Wood 109 Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control from Manufacturer to Consumer, Fifth Edition, Revised and Expanded, Sidney H Willig 110 Advanced Pharmaceutical Solids, Jens T Carstensen 111 Endotoxins: Pyrogens, LAL Testing, and Depyrogenation, Second Edition, Revised and Expanded, Kevin L Williams 112 Pharmaceutical Process Engineering, Anthony J Hickey and David Ganderton 113 Pharmacogenomics, edited by Werner Kalow, Urs A Meyer and Rachel F Tyndale 114 Handbook of Drug Screening, edited by Ramakrishna Seethala and Prabhavathi B Fernandes 115 Drug Targeting Technology: Physical • Chemical • Biological Methods, edited by Hans Schreier 116 Drug–Drug Interactions, edited by A David Rodrigues 117 Handbook of Pharmaceutical Analysis, edited by Lena Ohannesian and Anthony J Streeter 118 Pharmaceutical Process Scale-Up, edited by Michael Levin 119 Dermatological and Transdermal Formulations, edited by Kenneth A Walters 120 Clinical Drug Trials and Tribulations: Second Edition, Revised and Expanded, edited by Allen Cato, Lynda Sutton, and Allen Cato III 121 Modern Pharmaceutics: Fourth Edition, Revised and Expanded, edited by Gilbert S Banker and Christopher T Rhodes 122 Surfactants and Polymers in Drug Delivery, Martin Malmsten 123 Transdermal Drug Delivery: Second Edition, Revised and Expanded, edited by Richard H Guy and Jonathan Hadgraft 124 Good Laboratory Practice Regulations: Second Edition, Revised and Expanded, edited by Sandy Weinberg 125 Parenteral Quality Control: Sterility, Pyrogen, Particulate, and Package Integrity Testing: Third Edition, Revised and Expanded, Michael J Akers, Daniel S Larrimore, and Dana Morton Guazzo 126 Modified-Release Drug Delivery Technology, edited by Michael J Rathbone, Jonathan Hadgraft, and Michael S Roberts 127 Simulation for Designing Clinical Trials: A PharmacokineticPharmacodynamic Modeling Perspective, edited by Hui C Kimko and Stephen B Duffull 128 Affinity Capillary Electrophoresis in Pharmaceutics and Biopharmaceutics, edited by Reinhard H H Neubert and Hans-Hermann Rüttinger 129 Pharmaceutical Process Validation: An International Third Edition, Revised and Expanded, edited by Robert A Nash and Alfred H Wachter 130 Ophthalmic Drug Delivery Systems: Second Edition, Revised and Expanded, edited by Ashim K Mitra 131 Pharmaceutical Gene Delivery Systems, edited by Alain Rolland and Sean M Sullivan 132 Biomarkers in Clinical Drug Development, edited by John C Bloom and Robert A Dean 133 Pharmaceutical Extrusion Technology, edited by Isaac Ghebre-Sellassie and Charles Martin 134 Pharmaceutical Inhalation Aerosol Technology: Second Edition, Revised and Expanded, edited by Anthony J Hickey 135 Pharmaceutical Statistics: Practical and Clinical Applications, Fourth Edition, Sanford Bolton and Charles Bon 136 Compliance Handbook for Pharmaceuticals, Medical Devices, and Biologics, edited by Carmen Medina 137 Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products: Second Edition, Revised and Expanded, edited by Louis Rey and Joan C May 138 Supercritical Fluid Technology for Drug Product Development, edited by Peter York, Uday B Kompella, and Boris Y Shekunov 139 New Drug Approval Process: Fourth Edition, Accelerating Global Registrations, edited by Richard A Guarino 140 Microbial Contamination Control in Parenteral Manufacturing, edited by Kevin L Williams 141 New Drug Development: Regulatory Paradigms for Clinical Pharmacology and Biopharmaceutics, edited by Chandrahas G Sahajwalla 142 Microbial Contamination Control in the Pharmaceutical Industry, edited by Luis Jimenez 143 Generic Drug Product Development: Solid Oral Dosage Forms, edited by Leon Shargel and Izzy Kanfer 144 Introduction to the Pharmaceutical Regulatory Process, edited by Ira R Berry 145 Drug Delivery to the Oral Cavity: Molecules to Market, edited by Tapash K Ghosh and William R Pfister 146 Good Design Practices for GMP Pharmaceutical Facilities, edited by Andrew Signore and Terry Jacobs 147 Drug Products for Clinical Trials, Second Edition, edited by Donald Monkhouse, Charles Carney, and Jim Clark 148 Polymeric Drug Delivery Systems, edited by Glen S Kwon 149 Injectable Dispersed Systems: Formulation, Processing, and Performance, edited by Diane J Burgess 150 Laboratory Auditing for Quality and Regulatory Compliance, Donald Singer, Raluca-Ioana Stefan, and Jacobus van Staden 151 Active Pharmaceutical Ingredients: Development, Manufacturing, and Regulation, edited by Stanley Nusim 152 Preclinical Drug Development, edited by Mark C Rogge and David R Taft 153 Pharmaceutical Stress Testing: Predicting Drug Degradation, edited by Steven W Baertschi 154 Handbook of Pharmaceutical Granulation Technology: Second Edition, edited by Dilip M Parikh 155 Percutaneous Absorption: Drugs–Cosmetics–Mechanisms–Methodology, Fourth Edition, edited by Robert L Bronaugh and Howard I Maibach 156 Pharmacogenomics: Second Edition, edited by Werner Kalow, Urs A Meyer and Rachel F Tyndale 157 Pharmaceutical Process Scale-Up, Second Edition, edited by Michael Levin 158 Microencapsulation: Methods and Industrial Applications, Second Edition, edited by Simon Benita 159 Nanoparticle Technology for Drug Delivery, edited by Ram B Gupta and Uday B Kompella 160 Spectroscopy of Pharmaceutical Solids, edited by Harry G Brittain 161 Dose Optimization in Drug Development, edited by Rajesh Krishna 347 Index [Nanospheres] nanocarriers for restenosis, 237 plain polymethyl methacrylate, 18–19 polystyrene, 18 silica, 19 silver, 19 Nanostructured drug microparticles aerosol flow reactor method multicomponent drug synthesis, 113–114 peptide coating particles, 122–125 reactor drug crystallization, 121–122 Nanostructured lipid carriers (NLC), 214–216 chemical protection, 224 controlled-release properties, 222–223 cosmetic products, 213, 215, 226–229 creams, 221–222 entrapment efficiency, 222–223 gels, 220–221 hydration, 224–226 loading capacity, 222–223 morphology and structure, 218–219 occlusive effects, 224–226 penetration enhancement, 226 physical stability, 221–222 production, 220–221 skin effects, 221–226 transdermal products, 219–221, 227–229 types, 218–219 Nanostructured materials, 21 Nanostructured monoliths, 22 Nanosuspensions clofazimine, 75 vs liposomal form, 75 dermal, 76 injectable monocyte phagocytic system, 40 liposomal, 75 parenteral delivery, 33–46 combination of component technologies, 34 combined precipitation/homogenization, 36 formulation approaches, 34–36 formulation selection, 36 historical introduction, 33–34 homogenization, 35 injectable nanosuspension safety, 38–40 intrathecal delivery, 46 manufacturing methods, 34–36 molecular determinants of particle size, 36–37 parenteral formulation applications, 40–45 pharmacokinetic profiles, 37–38 pharmacokinetics, 44 precipitation, 35 [Nanosuspensions parenteral delivery] predecessor technology, 33 prediction of stability, 36–38 in vitro dissolution, 37 Taxol®, 34, 44 Nanotechnology, development, 162–163 diverse and emerging trends, 20–23 Nanotherapeutic applications biological requirements, 159–170 Nanotherapeutic devices, 166–168 Nanotubes carbon, 20, 169 cellular manipulation, 21 Nanowires silicon-based, 169 Naproxen physical properties, 118 Nasal immunization, 319–322 Natural and synthetic polymers, 51–59 in vitro cell culture, 58–59 New chemical entities (NCE), 77 Nitric oxide eluting stents nanofibers, 180 NK911, 180 NLC See Nanostructured lipid carriers (NLC) Nonviral vectors, 201–202 Normalization window, 148 NP gene transfection, 293 poly(D,L-lactic acid)-based formulation characteristics, 291–298 restenosis local drug delivery, 237 nanocarriers, 237 polymeric gene delivery, 242–243 NPDDS See Nanoparticle drug delivery systems (NPDDS) Nucleic acids, 161–162 Octylglucoside, 90 Ocular applications drug nanocrystals, 76 lipids, 278 NPDDS, 193–194, 271–279 Oil-in-water emulsion, 111 Oligodeoxyribonucleotides (ODN), 93 Oncology, 197–198 nanobiotechnology, 176 photodynamic therapy, 14 Ophthalmic drugs, 193 348 Opsinization, 142 Optical tweezers, Oral delivery drug nanocrystals, 74 Oral drug administration, 164 Oral immunization, 319 Oswald ripening, 78 PAA See Polyacrylic acid (PAA) PACA See Polyalkyl-cyanoacrylates (PACA) Paclitaxel, 249 local delivery for arterial localization, 248–249 parenteral formulations, 40–45 characterization and manufacture, 44 supersaturable formulation, 309 Palm oil, 101 Parenteral Abraxane® characterization and manufacture, 44 clinical trials, 44–45 pharmacokinetics, 44 Parenteral formulations anticancer, 44–45 antifungal, 42–43 clinical study, 43–44 drug nanocrystals, 74 intravenous, 41–42 preclinical studies drug-resistant fungal stain, 42–43 drug-susceptible fungal stain, 42 regional anesthetics, 39–41 Parenteral immunization, 318–319 Parenteral paclitaxel, 318–319 characterization and manufacture, 44 Parenteral Taxol® clinical trials, 44–45 Particle formation experimental parameters, 118 Passive tissue targeting drug-delivery system nanoengineering, 106 Passive tumor targeting metallic NDDS, 149 PBCA See Polybutylcyanoacrylate (PBCA) PC See Phosphatidylcholines (PC) P-channel MOSFET fabrication, 165 PCI See Percutaneous coronary intervention (PCI) PCNA See Proliferating cell nuclear antigen (PCNA) PDGF See Platelet-derived growth factor (PDGF) Index Pectin, 272, 273 PECVD See Plasma-enhanced vapor deposition (PECVD) PEG See Polyethylene glycol (PEG) PEI See Polyethylenimine (PEI) Penetration defined, 327–328 PEO See Polyethylene oxide (PEO) Peptide coating particles nanostructured drug microparticles, 121–122 Peptides NPDDS, 188–193 Percutaneous adsorption, 328 Percutaneous coronary intervention (PCI), 235 restenosis, 180 Perfume, 228 Permeation defined, 328 Peroxisomes, 160 Personalized medicine nanobiotechnology, 181 Peyer’s patches, 305, 306, 320 Phagocytic system monocytes injectable nanosuspension, 40 Phase-inversion-based technique, 217 Phase separation, 111 Phosphatidylcholines (PC), 92 Phosphorotioated oligodeoxynucleotides (PT-ODN), 239–240, 244 Photodynamic therapy cancer, 14 Photosensitizers, 14 Photothermal tumor ablation, 179 PillCam™, 178 Piston-gap homogenization in water drug nanocrystals, 79 Plain polymethyl methacrylate nanospheres, 18–19 Plasma cell membrane, 159 Plasma-enhanced vapor deposition (PECVD), 166 Plasmid DNA PLGA, 297 Platelet-derived growth factor (PDGF), 235, 243–244, 263 Platelets, 144–145 PLG See Polyglycolide (PLG) PLGA See Polylactide-co-glycolide (PLGA) PLGA-PEG See Polylactide-co-glycolide polyethylene glycol (PLGA-PEG) 349 Index PMA See Polymethacrylate (PMA) PMMA See Polymethyl methacrylate (PMMA) Poly(D,L-lactic acid) formulation characteristics, 277–278 Poly(D,L-lactide-co-glycolide), 277–278 Poly(epsilon-caprolacton), 276 Polyacrylic acid (PAA), 275 IPN, 200 isopropylacrylamide, 200 Polyalkyl-cyanoacrylates (PACA), 54, 274–277 gene delivery, 299 Polyanhydrides, 53 Poly(beta-amino ester)-based nanoparticles gene delivery, 299 Poly(D,L-lactic acid)-based NP formulation characteristics, 291–297 Polybutylcyanoacrylate (PBCA) cyclophosphamide-loaded, 193 nanoparticles, 288 Polycarbonate membrane, 90 Poly-ε-caprolactones, 53 Polyester polysaccharide nanoparticles, 16 Polyethylene glycol (PEG), 143 Polyethylene oxide (PEO), 295 Polyethylenimine (PEI), 298 Polyglycolide (PLG), 237 Polylactide, 53 Polylactide-co-glycolide (PLGA), 53, 186–187, 297, 307 molecular weight, 295 nanoparticles, SEM, 57 plasmid DNA, 297 Polylactide-co-glycolide polyethylene glycol (PLGA-PEG) formulation, 196 Polymer(s) natural origin, 272–274 Polymer-based nanoparticulate drug-delivery systems, 12–18 Polymeric drug nanoparticles aerosol flow reactor method, 114–116 Polymeric growth inhibitors, 78 Polymeric micelles drug solubilization, 10–11 research trends, 12 Polymeric nanocapsular-based drug-delivery systems lymphatic targeting, 306–312 Polymeric nanocapsules drug carriers, 17 Polymeric nanoparticulate-based drug-delivery systems aerosol flow reactor method, 113–114 gene delivery schematic representation, 269 lymphatic targeting, 305 preparation, 56 Polymethacrylate (PMA), 53 Polymethyl methacrylate (PMMA), 53 Polystyrene nanospheres, 18 Polyvinyl caprolactone nanoparticles, 53 Poorly soluble drugs solubilization, 71–85 Precipitation drug nanocrystals, 78, 83–84 evaporative, 111 Progesterone supercooled smectic nanoparticles, 135–136 Proliferating cell nuclear antigen (PCNA), 239 Propofol, 17 Prosthetics nanoengineered, 21 Protamine-based nanoparticulate drug carriers, 14–15 Protective nanoparticles against pathogens, 21 Proteins cells, 162 NPDDS, 188–193 Proticles, 14–15, 197 PT-ODN See Phosphorotioated oligodeoxynucleotides (PT-ODN) Pullulan, 53, 202 Pulmonary drug delivery, 193–195 drug nanocrystals, 96 Quantum dots, 169 drug discovery, 175–176 molecular diagnostics, 173–174 Rapamune®, 78 Rapamycin, 236 Reactor drug crystallization nanostructured drug microparticles, 121–122 Receptor-mediated transcytosis, 286–287 Regional anesthetics parenteral formulations, 40–41 RES See Reticuloendothelial system (RES) Restenosis, 235 dexamethasone, 245–246 gene therapy, 239–240 liposomal gene delivery, 240–242 350 [Restenosis] local delivery formulation, 246 local drug delivery, 237–238, 243–246 nanocarriers, 235–256 polymeric NP gene delivery, 242–243 systemic drug delivery, 248–255 arterial localization, 248–249 for systemic target, 249–251 Reticuloendothelial system (RES), Retinoic acid, 278 Rhodamine, 253 nanoparticles containing, 238 RH-targeted silica-coated lipid micelles, 169 Ribosomes, 159 Rolipram, 313 Rough endoplasmic reticulum, 159–160 Salting-out, 111 Scanning electron microscopy (SEM), Scanning probe microscopy (SPM), Self-diagnostics, 181 Self-(micro) emulsifying drug-delivery systems lymphatic targeting, 309–312 SEM See Scanning electron microscopy (SEM) Shaving aids, 227 Silica-coated lipid micelles LH-RH-targeted, 169 Silica nanospheres, 19 Silicon-based nanowires, 169 Silicone nanopore-membrane-based drug-delivery system, 15 Silicon nanoparticles anti-HER2 antibody-targeted, 169 Silver nanospheres, 19 Silver powder antimicrobial properties, 181 Single-beam gradient trap, Single-molecule detection, 21 SiRNA, 93 Skin aging, 227 permeation test, 327, 332, 334 SLN See Solid-lipid nanoparticles (SLN) Small-scale cyclone, 116 SMC See Smooth muscle cells (SMC) Smectic nanoparticles preparation methods, 132 Smooth endoplasmic reticulum, 160 Smooth muscle cells (SMC), 235 Sodium chloride SEM, 125 Index Sodium leucine SEM, 125 Sol-gel process, 164–165 Solid-lipid nanoparticles (SLN), 5, 54, 188, 214 brain, 287–288 chemical protection, 224 controlled-release properties, 222–224 cosmetic products, 219–221 creams, 221 entrapment efficiency, 222–224 gels, 220–221 hydration, 224–226 loading capacity, 222–224 lymphatic targeting, 308 morphology and structure, 218–219 occlusive effects, 224–226 ocular applications, 278 penetration enhancement, 225 physical stability, 221–222 production, 216–218 research trends, 7–9 skin effects, 221–229 transdermal products, 219–220 types, 219 Solvent displacement method, 217 SPIO See Superparamagnetic iron oxide (SPIO) SPM See Scanning probe microscopy (SPM); Sulfopropylmethacrylate (SPM) Sporanox®, 42–44, 72 vs itraconazole, 43 parenteral administration, 75 Spray-drying, 84, 112–113 Starch, 14 Starch acetate, 272 Stem-cell-based therapies nanobiotechnology, 178 Stents drug-eluting, 235 Sterically stabilized liposomes formulation strategies, 92 Stratum corneum adsorption, 328 Subcutaneous drug administration, 164 Sulfopropylmethacrylate (SPM), 275 Supercooled smectic nanoparticles, 129–138 CM nanoparticles properties and phase behavior, 133–137 ultrastructure, 136, 138 etomidate, 135 ibuprofen, 135 matrix composition, 133–135 model drugs, 135–136 preparation methods, 132 351 Index [Supercooled smectic nanoparticles] stabilizer system, 132–133 thermotropic mesophases, 130 Superparamagnetic iron oxide (SPIO), 150 Sustained-released systems drug-delivery system nanoengineering, 99–101, 102–103 modulation of drug environment, 102–103 physicochemical properties, 102–103 polymeric drug-delivery system, 99–101 Sustained-release electrospun fibers nanofiber-based drug delivery, 64–65 Synthetic nanodevices, 177 TAM See Tumor-associated macrophages (TAM) Targeted drug delivery, 176 Targeted liposomes formulation strategies, 94 Taxol® vs Abraxane®, 44 nanosuspensions, 33–34 parenteral formulations clinical trials, 44–45 TAXUS®, 236 TEM See Transmission electron microscopy (TEM) Temperature-sensitive liposomes formulation strategies, 93 TGA See Thermogravimetric analysis (TGA) Thermal ablation tumor-targeting metallic nanoparticle drug-delivery systems, 152–153 Thermogravimetric analysis (TGA), 56 Thermosensitive nanoparticles, 54 Thermotropic calamitic mesophases structure, 130 Thiamine-targeted nanoparticles, 169 Thiomer nanoparticles, 21 Tissue factor, 237 TNF See Tumor necrosis factor (TNF) TNT system, 169 Tobramycin, 310, 312–313 SLN, 278 Transcytosis receptor-mediated, 286–287 Transdermal applications, 327–335 future, 335 limitations, 334–335 Transfersomes, 169 Transmission electron microscopy (TEM), Triacylglycerols three-dimensional structure, 215 TriCor®, 78 Triggered-released systems drug-delivery system nanoengineering, 99–103 modulation of drug environment and physicochemical properties drug-delivery system nanoengineering, 102–103 polymeric drug-delivery system drug-delivery system nanoengineering, 99–100 Tumor(s) blood vessels, 145 photothermal ablation, 179 Tumor-associated macrophages (TAM), 145 Tumor necrosis factor (TNF), 148, 241 Tumor-targeting metallic nanoparticle drug-delivery systems, 141 active vs passive tumor targeting, 149 angiogenic tumor blood vessels, 146–147 chemistry, 151 cytokine-mediated reduction of interstitial fluid pressure, 150 gold nanoparticles, 150 studies, 151–152 intratumor barriers, 149 iron nanoparticles, 150 studies, 152 multifunctional nanoparticles, 153–154 RES clearance, 142–144 safety, 150–151 thermal ablation, 152 tumor angiogenesis and interstitial fluid pressure, 148 and vascularization, 144–145 tumor models, 149–150 vascular endothelial growth factor, 145–146 Tweezers optical, Tyrphostins local delivery for restenosis, 243–245 U86 See 2-Aminochromone U-86893 (U86) Ultra-small superparamagnetic iron oxide (USPIO), 150 Ultraviolet blockers, 227, 228 Vaccination adjuvant-vector, 317–323 Vascular endothelial growth factor (VEGF) tumor-targeting metallic nanoparticle drug-delivery systems, 145–146, 150 352 Vascular smooth muscle cells (VSMC), 239 Vascular thrombosis, 198–199 Vasculogenesis, 146 Vasoactive intestinal peptide (VIP), 194 Vectors nonviral, 201 VEGF See Vascular endothelial growth factor (VEGF) Verteprofin liposomal, 90 Vesicular vacuolar organelles (VVO), 145 VIP See Vasoactive intestinal peptide (VIP) Index Virosome, 241–242 von Willebrand factor, 144 VVO See Vesicular vacuolar organelles (VVO) Water-in-oil-in-water double emulsion, 292 Water-soluble amphiphilic nanocarriers freeze drying, 11 Wet milling, 111 Whole skin penetration, 332–334 Zeldox®, 72 Zeta potential nanoparticles, 57 FIGURE 1.1 Length scale showing the nanometer in context The length scale of interest for nanoscience and nanotechnologies is from 100 nm down to the atomic scale approximately 0.2 nm Source: From Ref FIGURE 3.2 Schematic diagram of specific receptor targeting of nanospheres using ligands FIGURE 4.6 Results of automated fiber size analysis FIGURE 5.5 Two nanosuspensions composed similarly, produced by high-pressure homogenization, conventional method (left ) versus translucent nanosuspension (particle size well below 100 nm) resulting from H96 technology The red laser beam is reflected by the tiny nanocrystals Source : From Ref 40 FIGURE 11.1 Structure of a typical cell FIGURE 13.1 Different types of nanoparticulate structures FIGURE 14.1 Basic types of solid nanoparticles and nanostructured lipid center Abbrevations: NLC, nanostructured lipid carrier; SLN, solid–lipid nanoparticle Source: From Ref 44 FIGURE 15.1 Confocal images of balloon-injured rat carotid arteries after intaluminal delivery of rhodamine solution and rhodamine-containing nanoparticles The arteries were harvested 90 minutes (A and D), eight hours (B and E), and one day (C and F) after delivery Source: From Ref 108 FIGURE 15.2 (A) Inhibition of neointimal formation 14 days after balloon injury to rat carotid artery and intraluminal instillations with 20 μM (1nmole) antisense or scrambled partially phosphorothioated oligodeoxynucleotides (PT-ODNs) encapsulated in PLGA nanoparticles (total of 50 μL suspension) Photomicrographs of representative histological sections Verchoeff’s elastin stain, magnification ×12.5 (B) Fluorescence micrographs of blank and PT-ODN-loaded PLGA nanoparticles The PTODNs were covalently labeled with FITC prior encapsulation Note fluorescence signal in over 90% of the particles Abbreviations: A, adventitia; L, lwnen; M, media; N, neointima; NP, nanoparticles; SC-NP, scrambled NP; AS-NP, antisense NP Source: From Refs 198 and 201 FIGURE 15.3 (C) Low- and high-power photomicrographs of hypercholesterolemic rabbit iliac artery stents at 28 days (Verhoeff staining) of control (I and II) and of animals treated with LA mg/kg (III and IV) and mg /kg (V and VI) Abbreviation: LA, liposomal alendronate Source : From Refs 269 and 292 FIGURE 18.2 Formulation factors influencing nanoparticle-mediated gene expression Abbreviations: NPs, nanoparticles; PE, primary endosomes; RE, recycling endosomes FIGURE 20.1 Visualization of flagellin-coated nanoparticles (red dots) in the follicle-associated epithelium of Peyer’s patches by fluorescence Flagellin of S enteritidis was used to coat Gantrez nanoparticles (labeled with rhodamine B isothiocyanate) and, thus, obtaining adjuvant vectors able to spread within the gut in a similar way than the whole bacteria Source: From Ref 34 FIGURE 21.1 Cryo-sectioned images of the fluorescent labeled nanoparticulate with porcine epidermal skin layer after in vitro skin permeation test (A) Stratum comeum outer layer adsorption of 200 nm-sized polysturene nanoparticulate (B) Percutaneous absorption of 40 nm-sized polystyrene nanoparticulate (C) Epidermal layer penetration of the modified nanoparticulate Abbreviations: EP, epidermis; SC, stratum comeum FIGURE 21.2 CLSM images of the nanoparticulate penetration with a guinea pig skin (cryosectioned) Fluorescent-labelled nanoparticulate (green region), nuclei-labeled DAPI (blue region) (A) 40 nm size of nanoparticles, (B) 130 nm size of nanoparticles (10 pieces of z-direction sectioning image of cross sectioned tissue are merged) Nanoparticulate: Polycaprolactone-polyethyleneglycol block copolymer aggregates Fluorescent: Rubrene Source: From Ref 27 FIGURE 21.3 Images of the liposome nanoparticulate with fluorescent by in vitro permeation test with a guinea pig skin (A) RITC saturated solution (B) RITC with the modified liposome (Red region), hydrophilic fluorescent dye (RITC); (blue region), DAPI for nuclei; basal layer (white arrows) FIGURE 21.4 Fluorescent images of in vivo permeation study with Albino Hartley guinea pig (A) O/W emulsion formulation (B) Modified polymeric nanoparticulate ... and lipid-based nanoparticulate drug- delivery systems, respectively Chapters to 10 discuss the engineering aspects and different techniques used for nanoparticulate drug- delivery systems, including... area of nanoparticulate drug- delivery systems The first chapter covers a complete overview of the nanoparticulate drugdelivery system, covering wide applications and evaluation of the nanoparticulate. .. define drug- delivery systems of a certain size range Reflecting this trend of size definition, Nanoparticulate Drug Delivery Systems is a worthy attempt to bring together a wide range of drug- delivery