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Book Details
Abstract
Drug delivery systems and pharmaceutical nanocarriers that respond to different types of stimuli, such as internal ones, intrinsic for the pathological area (changes in pH, temperature, redox condition, activity of certain enzymes), or external, artificially applied (magnetic field, ultrasound, various irradiations), represent an important and continuously growing area of research. Smart Phramaceutical Nanocarriers overviews the various stimuli used for drug release and delivery by smart pharmaceutical carriers and presents cutting-edge research and the newest data from the leading laboratories in each area.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Contents | ix | ||
| Preface | v | ||
| Chapter 1 Stimuli-Sensitive Nanopreparations: Overview | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 Stimuli Characteristics for Pathological Tissues (see Table 1.1) | 3 | ||
| 1.2.1 pH | 3 | ||
| 1.2.2 Reduction–oxidation (redox) potential | 6 | ||
| 1.2.3 Locally overexpressed enzymes | 9 | ||
| 1.2.4 Temperature | 12 | ||
| 1.3 Stimuli Acting from Outside of the Body (see Table 1.1) | 15 | ||
| 1.3.1 Magnetic field | 15 | ||
| 1.3.2 Light | 26 | ||
| 1.3.3 Ultrasound | 28 | ||
| 1.4 Concluding Remarks | 30 | ||
| References | 31 | ||
| Chapter 2 pH-Sensitive Nanosystems | 49 | ||
| 2.1 Introduction | 49 | ||
| 2.2 Mechanism of pH-Sensitivity | 51 | ||
| 2.2.1 Protonation/deprotonation | 51 | ||
| 2.2.2 Acid-labile bonds | 54 | ||
| 2.3 Representative pH-Sensitive Nanosystems | 56 | ||
| 2.3.1 Micelle | 56 | ||
| 2.3.2 Liposome | 59 | ||
| 2.3.3 Mesoporous silica nanoparticles | 59 | ||
| 2.3.4 Others | 61 | ||
| 2.4 pH-Sensitive Nanosystems for Drug Delivery | 61 | ||
| 2.4.1 Delivery of small molecule drugs | 61 | ||
| 2.4.2 Gene delivery | 66 | ||
| 2.4.3 Protein/peptide delivery | 68 | ||
| 2.5 Other Applications of pH-Sensitive Nanosystems | 69 | ||
| 2.5.1 Imaging | 69 | ||
| 2.5.2 pH measurement | 70 | ||
| 2.5.3 Miscellaneous | 73 | ||
| 2.6 Conclusion and Perspective | 73 | ||
| Acknowledgement | 74 | ||
| References | 74 | ||
| Chapter 3 Matrix Metalloproteinase-Sensitive Nanocarriers | 83 | ||
| 3.1 Introduction | 83 | ||
| 3.2 MMPs and their Physiological Functions | 85 | ||
| 3.3 Up-Regulation of MMPs in Pathological Conditions | 86 | ||
| 3.4 Design of MMP-Sensitive Nanosized Drug \rDelivery and Imaging Systems | 87 | ||
| 3.4.1 Substrates for MMPs | 87 | ||
| 3.4.2 MMP-sensitive drug conjugates | 91 | ||
| 3.4.3 MMP-sensitive liposomal nanocarriers | 94 | ||
| 3.4.4 MMP-sensitive polymeric micelles | 96 | ||
| 3.4.5 MMP-sensitive protein-based nanoparticles | 99 | ||
| 3.4.6 Dendrimer-based nanoparticles | 100 | ||
| 3.4.7 MMP-sensitive nanogels | 101 | ||
| 3.4.8 Other polymeric nanoparticles sensitive to MMPs | 103 | ||
| 3.4.9 MMP-sensitive inorganic nanoparticles | 104 | ||
| 3.4.10 MMP-sensitive multifunctional nanocarriers | 105 | ||
| 3.5 Challenges and Future Directions | 107 | ||
| References | 108 | ||
| Chapter 4 Redox-Sensitive Nanosystems | 117 | ||
| 4.1 Introduction | 117 | ||
| 4.2 Redox-Sensitive Polyethylenimines (PEIs) | 119 | ||
| 4.3 Redox-Sensitive Polypeptides | 124 | ||
| 4.4 Redox-Sensitive Poly(amido amine)s | 127 | ||
| 4.5 Redox-Sensitive Polyion Complex (PIC) Micelles | 132 | ||
| 4.6 Redox-Sensitive nanogels | 133 | ||
| 4.7 Summary and Future Perspective | 136 | ||
| Acknowledgements | 136 | ||
| References | 136 | ||
| Chapter 5 Temperature-Sensitive Pharmaceutical Nanocarriers | 143 | ||
| 5.1 Introduction | 143 | ||
| 5.2 Pharmaceutical Nanocarriers: The Need for Targeted and Triggered Drug Delivery \r | 144 | ||
| 5.3 Passive/Active Targeting of Nanocarriers | 146 | ||
| 5.4 Functional Properties of Thermo-Sensitive Polymers and Lipids | 149 | ||
| 5.4.1 Thermo-sensitive polymers | 149 | ||
| 5.4.2 Thermo-sensitive lipids | 151 | ||
| 5.5 Thermo-Sensitive Micelles | 153 | ||
| 5.6 Thermo-Sensitive Hydrogels | 158 | ||
| 5.7 Thermo-Sensitive Liposomes | 159 | ||
| 5.8 Modalities for Hyperthermia Application | 167 | ||
| 5.9 Future Perspectives | 168 | ||
| References | 168 | ||
| Chapter 6 Ultrasound-Controlled Nanosystems | 179 | ||
| 6.1 Introduction | 179 | ||
| 6.2 Structure and Properties of Ultrasound-Controlled \rNanosystems | 180 | ||
| 6.2.1 Polymer-shelled nanoparticles | 181 | ||
| 6.2.1.1 Polymer micelles | 182 | ||
| 6.2.1.2 Polymer-shelled microbubbles | 183 | ||
| 6.2.2 Liposomes | 183 | ||
| 6.2.2.1 Temperature-sensitive liposomes | 183 | ||
| 6.2.2.2 Liposome-shelled nanobubbles | 185 | ||
| 6.2.3 Protein-shelled microbubbles | 186 | ||
| 6.3 Active Targeting of Ultrasound-Responsive Nanoparticles | 186 | ||
| 6.3.1 Targeting strategies | 187 | ||
| 6.3.2 Targeted nanoparticle evaluation | 190 | ||
| 6.4 Therapeutic Ultrasound | 191 | ||
| 6.4.1 Biophysics of therapeutic ultrasound | 191 | ||
| 6.4.2 Cavitation | 192 | ||
| 6.4.3 Acoustic radiation force | 192 | ||
| 6.4.4 Thermal bioeffects | 193 | ||
| 6.4.5 Acoustic parameters for enhanced therapeutic delivery | 193 | ||
| 6.4.5.1 Peak rarefactional pressure and center frequency | 193 | ||
| 6.4.5.2 Pulse duration and duty cycle | 193 | ||
| 6.5 Therapeutic Applications of Ultrasound-Controlled \rNanosystems | 194 | ||
| 6.5.1 Drug and gene delivery to the brain | 194 | ||
| 6.5.2 Drug and gene delivery to the kidneys | 195 | ||
| 6.5.3 Drug and gene delivery to the lungs and the pleural space | 196 | ||
| 6.5.4 Gene therapy applications | 196 | ||
| 6.5.5 Drug and gene delivery in atherosclerosis and myocardium | 198 | ||
| 6.5.5.1 Atherosclerosis | 198 | ||
| 6.5.5.2 Myocardium | 199 | ||
| 6.5.6 Bioactive gas delivery | 199 | ||
| 6.6 Conclusions | 200 | ||
| References | 200 | ||
| Chapter 7 Plasmonic Nanobubble-Controlled On Demand Drug Delivery and Release with High Target Cell Specificity | 213 | ||
| 7.1 Introduction | 213 | ||
| 7.2 Generation and Detection of PNBs | 215 | ||
| 7.2.1 Mechanism of PNB generation | 219 | ||
| 7.3 Target Cell Specificity of PNB vs. NPS | 223 | ||
| 7.4 PNB-Induced Ejection (Release) of an Encapsulated Payload | 228 | ||
| 7.5 Therapeutic Responses to Drugs, GNPs, Laser Pulses and X-Rays In Vitro | 230 | ||
| 7.6 The Mechanism of Intracellular Self-Amplification of the Therapeutic Strength with Cancer Aggressiveness | 233 | ||
| 7.7 Generation and Detection of PNBs In Vivo | 234 | ||
| 7.8 The Evaluation of PNB Therapy and Diagnostics In Vivo | 237 | ||
| 7.9 Future Medical Applications of PNBs | 241 | ||
| References | 243 | ||
| Chapter 8 Light-Activated Nanopreparations | 253 | ||
| 8.1 Introduction | 253 | ||
| 8.2 Light-Modulated Self Assembly | 254 | ||
| 8.3 Photo-Responsive Molecules | 255 | ||
| 8.4 Vehicles for Light-Activated Drug Delivery | 257 | ||
| 8.4.1 Liposomes | 257 | ||
| 8.4.2 Micelles | 259 | ||
| 8.4.3 Nanoparticles | 260 | ||
| 8.5 Challenges | 261 | ||
| 8.6 Conclusions | 261 | ||
| References | 262 | ||
| Chapter 9 Magnetic Field-Responsive Nanocarriers | 267 | ||
| 9.1 Introduction | 267 | ||
| 9.2 Magnetic Materials and Nanoparticles: A Brief Overview | 268 | ||
| 9.2.1 Properties and types of magnetic materials | 269 | ||
| 9.2.2 Commonly employed magnetic materials | 270 | ||
| 9.3 Magnetic Drug Targeting (MDT) Using Nanocarriers: General Concepts | 272 | ||
| 9.4 Magnetically Responsive Nanocarriers for Specific Applications | 275 | ||
| 9.4.1 Passively targeted magnetic nanocarriers | 275 | ||
| 9.4.2 Actively targeted magnetic nanocarriers | 278 | ||
| 9.4.3 MFRNs for hyperthermia | 280 | ||
| 9.4.4 Magnetic field-responsive nanocarriers for imaging | 285 | ||
| 9.4.5 Magnetic field-responsive nanocarriers as theranostics | 288 | ||
| 9.4.6 Other biomedical applications of MNPs\r | 291 | ||
| 9.5 Multifunctional Magnetic Nanocarriers | 292 | ||
| 9.6 Conclusion and Future Perspectives | 295 | ||
| References | 296 | ||
| Chapter 10 Smart Lipid-Based Drug Delivery Systems | 309 | ||
| 10.1 Introduction | 309 | ||
| 10.2 Smart Lipid-Based Carriers for Systemic Drug Delivery | 314 | ||
| 10.2.1 Smart liposomes for systemic delivery | 314 | ||
| 10.2.1.1 First generation of liposomes: Plain liposomes | 314 | ||
| 10.2.1.2 Long-circulating liposomes: “Stealth” liposomes | 315 | ||
| 10.2.1.3 Long-circulating functionalized liposomes for active targeting | 317 | ||
| 10.2.1.4 pH-responsive liposomes | 318 | ||
| 10.2.1.5 Temperature-responsive liposomes: Thermoliposomes | 319 | ||
| 10.2.1.6 Redox-responsive liposomes | 319 | ||
| 10.2.1.7 Magnetically-responsive liposomes: Magnetoliposomes | 320 | ||
| 10.2.1.8 Ultrasound-responsive liposomes: Ultrasonic liposomes | 321 | ||
| 10.2.1.9 Light-responsive liposomes | 322 | ||
| 10.2.1.10. Cationic liposomes: Lipid-DNA complexes for gene delivery | 323 | ||
| 10.2.2 Smart lipid-based micelles for systemic delivery | 328 | ||
| 10.2.3 Smart SLNs for systemic delivery | 329 | ||
| 10.2.4 Smart LNCs for systemic delivery | 330 | ||
| 10.2.5 Smart lipid-coated systems for systemic delivery | 332 | ||
| 10.2.5.1 Lipid-coated gas microbubbles | 332 | ||
| 10.2.5.2 LPHNs | 332 | ||
| 10.2.6 Smart oil-in-water emulsions for systemic delivery | 334 | ||
| 10.3 Smart Lipid-Based Carriers for Oral Drug Delivery | 336 | ||
| 10.3.1 Smart liposomes for oral delivery | 338 | ||
| 10.3.2 Smart lipid-based liquid crystals for oral delivery | 339 | ||
| 10.3.3 Smart long-chain triglyceride or fatty acid-based delivery systems for oral delivery | 341 | ||
| 10.3.4 Smart SMEDDSs for oral delivery | 343 | ||
| 10.4 Smart Lipid-Based Carriers for Dermal and Transdermal Delivery | 345 | ||
| 10.4.1 Smart liposomes for transdermal delivery | 345 | ||
| 10.4.2 Smart lipid-based liquid crystals for dermal delivery | 346 | ||
| 10.4.3 Smart solid lipid nanoparticles for dermal delivery | 347 | ||
| 10.5 Smart Lipid-Based Carriers for Ocular Delivery | 347 | ||
| 10.5.1 Smart liposomes for ocular delivery | 348 | ||
| 10.5.2 Smart solid lipid nanoparticles for ocular delivery | 348 | ||
| 10.6 Smart Lipid-Based Carriers for Intramuscular \rDelivery of Vaccines: Virosomes | 349 | ||
| r10.7 Summary | 350 | ||
| Acknowledgements | 351 | ||
| References | 351 | ||
| Chapter 11 Smart Polymer-Based Nanomedicines | 373 | ||
| 11.1 Polymer Therapeutics Design and Synthesis | 373 | ||
| 11.1.1 Polymer principles | 374 | ||
| 11.1.2 Early polymer therapeutics | 376 | ||
| 11.1.3 Incorporating smart functionality | 376 | ||
| 11.1.4 Synthesis strategies | 378 | ||
| 11.1.4.1 Atom Transfer Radical Polymerization (ATRP) | 378 | ||
| 11.1.4.2 Reversible Addition−Fragmentation Chain-Transfer (RAFT ) | 378 | ||
| 11.2 Stimuli | 379 | ||
| 11.2.1 Temperature | 379 | ||
| 11.2.2 pH | 381 | ||
| 11.2.3 Light | 383 | ||
| 11.2.4 Reduction | 383 | ||
| 11.2.5 Ultrasound | 384 | ||
| 11.3 Biorecognition/Biological | 384 | ||
| 11.3.1 Passive targeting | 385 | ||
| 11.3.2 Active targeting | 385 | ||
| 11.3.3 Selective targeting | 386 | ||
| 11.4 Structures of Polymer-Based Nanomedicines | 386 | ||
| 11.4.1 Linear polymers | 386 | ||
| 11.4.1.1 In vivo self-assembling polymer therapeutics | 390 | ||
| 11.4.2 Micelles | 392 | ||
| 11.4.3 Polymersomes | 393 | ||
| 11.4.4 Nanogels or shell cross-linked micelles | 395 | ||
| 11.4.5 Dendritic polymers | 397 | ||
| 11.4.6 Elastin-like polypeptides | 398 | ||
| 11.5 Challenges for Translation | 399 | ||
| 11.5.1 Necessary steps towards safe smart polymer therapeutics | 401 | ||
| 11.5.1.1 Biocompatibility | 402 | ||
| 11.5.1.2 Characterization of smart therapeutics | 402 | ||
| References | 403 | ||
| Chapter 12 Inorganic Nanoparticle-Based Smart Drug Delivery Systems | 415 | ||
| 12.1 Introduction | 415 | ||
| 12.2 Design Consideration of Inorganic NPs for Delivery Application | 416 | ||
| 12.2.1 HD size | 417 | ||
| 12.2.2 Surface charge | 422 | ||
| 12.2.3. Targeting | 427 | ||
| 12.3 Smart Delivery System with Strategic Payload Release | 430 | ||
| 12.3.1 pH | 430 | ||
| 12.3.2. Intracellular GSH | 433 | ||
| 12.3.3 Light | 436 | ||
| 12.3.4. Magnetic field | 438 | ||
| 12.4 Conclusion | 441 | ||
| References | 443 | ||
| Chapter 13 Smart Nanopreparations for Cancer | 449 | ||
| 13.1 Introduction | 449 | ||
| 13.1.1 pH-sensitive nanoformulation | 449 | ||
| 13.1.2 Gold nanoparticles | 454 | ||
| 13.1.2.1 AuNPs in drug delivery of lung cancer | 459 | ||
| 13.1.2.2 AuNPs for cytotoxicity studies | 460 | ||
| 13.1.2.3 Smart GNPs enhance killing effect on cancer cells | 461 | ||
| 13.1.2.4 Photodynamic therapy | 462 | ||
| 13.1.2.5. Diagnostics | 463 | ||
| 13.1.3 Magnetic nanoparticles | 465 | ||
| References | 470 | ||
| Chapter 14 Advances in Smart Nanopreparations for Oral Drug Delivery | 479 | ||
| 14.1 Introduction | 479 | ||
| 14.1.1 Importance of oral delivery and nanotechnology | 480 | ||
| 14.1.1.1 Side effects of drugs | 480 | ||
| 14.1.1.2 Biodisponibility of drugs | 481 | ||
| 14.1.2 Physiological barriers that affect nanopreparations’stability | 481 | ||
| 14.1.2.1 Gastric acidity | 481 | ||
| 14.1.2.2 GI proteases | 482 | ||
| 14.1.2.3 Transport mechanisms in the GI tract | 482 | ||
| 14.1.2.4 Mucus layer of GI tract | 482 | ||
| 14.1.2.5 Residence time | 483 | ||
| 14.1.3 Biopharmaceutical considerations | 483 | ||
| 14.1.3.1 Mononuclear phagocyte system (MPS)—PEGylation | 483 | ||
| 14.1.3.2 The enhanced permeation and retention (EPR) effect | 484 | ||
| 14.1.3.3 Active targeting | 484 | ||
| 14.2 Nanopreparations | 485 | ||
| 14.2.1. Nanocrystals | 485 | ||
| 14.2.1.1 Drug nanocrystals | 485 | ||
| 14.2.1.2 Cross-linked enzyme: Crystals (CLECs) and aggregates (CLEAs) | 488 | ||
| 14.2.2 Polymeric nanocarriers | 489 | ||
| 14.2.2.1. Polymeric nanoparticles | 491 | ||
| 14.2.2.2 Polymeric micelles | 493 | ||
| 14.2.2.3 Polymer–drug conjugates | 494 | ||
| 14.2.3 Emulsions | 495 | ||
| 14.2.3.1 Liposomes | 495 | ||
| 14.2.3.2 Solid lipid nanoparticles (SLNs) | 498 | ||
| 14.2.3.3 Nano-structured lipid carrier | 504 | ||
| 14.2.4. Inorganic and hybrid systems | 505 | ||
| 14.2.4.1 Silica | 506 | ||
| 14.2.4.2 Zeolites and Nanoclays | 508 | ||
| 14.2.4.3 Silver nanoparticles | 512 | ||
| 14.3 Conclusions | 514 | ||
| Acknowledgments and Conflict of Interest Statement | 514 | ||
| References | 515 | ||
| Chapter 15 Smart Theranostic Nanosystems | 523 | ||
| 15.1 Introduction | 523 | ||
| 15.2 pH-Sensitive Theranostic Nanosystems | 523 | ||
| 15.2.1 Mechanisms for pH sensitivity | 524 | ||
| 15.2.2 Strategies for targeting | 527 | ||
| 15.2.3 Application of pH-sensitive theranostics | 528 | ||
| 15.3 Photo-Responsive Systems | 530 | ||
| 15.3.1 Design and synthesis of PR theranostic nanoplatforms | 530 | ||
| 15.3.2 Gold-based PR theranostic tanosystems | 532 | ||
| 15.3.3 Silica-based and other PR theranostic nanosystems | 535 | ||
| 15.4 Magnetically Responsive Systems | 536 | ||
| 15.4.1 Design and synthesis of theranostic magnetic nanoplatforms | 539 | ||
| 15.4.2. Design parameters of magnetically responsive nanosystems | 539 | ||
| 15.4.3 Application of magnetic nanosystems | 541 | ||
| 15.5 Conclusion | 545 | ||
| Acknowledgement | 547 | ||
| References | 547 |