Functional Chitosan (eBook)
XII, 489 Seiten
Springer Singapore (Verlag)
978-981-15-0263-7 (ISBN)
Thanks to their unique properties, chitosan and chitosan-based materials have numerous applications in the field of biomedicine, especially in drug delivery. This book examines biomedical applications of functional chitosan, exploring the various functions and applications in the development of chitosan-based biomaterials. It also describes the chemical structure of chitosan and discusses the relationship between their structure and functions, providing a theoretical basis for the design of biomaterials. Lastly, it reviews chemically modified and composite materials of chitin and chitosan derivatives for biomedical applications, such as tissue engineering, nanomedicine, drug delivery, and gene delivery.
Sougata Jana is a B.Pharm (Gold Medalist) from West Bengal University of Technology, Kolkata, and M. Pharm (Pharmaceutics) from Biju Patnaik University of Technology, Odisha, India. He worked as an Assistant Professor at Gupta College of Technological Sciences, Asansol, West Bengal, India, and is currently working at the Department of Health and Family Welfare, Directorate of Health Services, Kolkata, India. He has been engaged in pharmaceutical education and research for the last 11 years. He was awarded the 'M. N Dev Memorial Award' by IPA Bengal branch, Kolkata, India, for securing the highest marks in the state of West Bengal in 2005. He received the 'Best Poster Presentation Award' at the 21st West Bengal State Science and Technology Congress, 2014, and 'Outstanding Paper Award' at the 1st Regional Science and Technology Congress, 2016, organized by DST, Govt. of West Bengal, India. He has 30 publications in different national and international peer-reviewed journals. He edited books in Springer, Elsevier, and Pharmamedix India Publication Pvt., Ltd., and has contributed more than 35 book chapters to Elsevier, Springer, Wiley VCH, CRC Press, and Taylor & Francis. His research area of interest includes modification of synthetic and natural biopolymers, microparticles, nanoparticles, semisolids, and interpenetrating polymer network system for controlled drug delivery.
Subrata Jana is presently working as an Associate Professor at the Department of Chemistry, Indira Gandhi National Tribal University (Central University), Amarkantak, Madhya Pradesh, India, and his current research focuses on the design and synthesis of artificial receptors for the recognition of anions, cations, and N-methylated protein residue. His other area of research interest is biodegradable polymeric-based carrier systems for the delivery of drug molecules. So far he has published -40 research papers in peer-reviewed international journals and contributed more than 10 book chapters to different edited books published by internationally renowned publishers. He is also an editorial board member in the Journal of PharmaSciTech (ISSN: 2231 3788) and the International Journal of Scientific and Engineering Research (ISSN: 2229-5518) and a reviewer in the International Journal of Biological Macromolecule (Elsevier), the Journal of PharmaSciTech, and Current Pharmaceutical Design (Bentham). He has obtained his PhD in organic chemistry from Indian Institute of Engineering Science and Technology (IIEST), Shibpur, India. Then he moved to the University of Victoria, Canada, to work with Professor (Dr.) Fraser Hof on supramolecular and medicinal chemistry as a postdoctoral fellow. He then worked further with Dr. Kenneth J Woycechowsky at the University of Utah, USA, on protein engineering and enzyme catalysis as a postdoctoral research associate. Overall he extensively studied on the supramolecular behavior of the host-guest interaction and synthesis of heterocyclics, such as pyrimidines, naphthyridines, quinoline, and diazepines, by exploiting microwave protocol for green chemical synthesis.
Thanks to their unique properties, chitosan and chitosan-based materials have numerous applications in the field of biomedicine, especially in drug delivery. This book examines biomedical applications of functional chitosan, exploring the various functions and applications in the development of chitosan-based biomaterials. It also describes the chemical structure of chitosan and discusses the relationship between their structure and functions, providing a theoretical basis for the design of biomaterials. Lastly, it reviews chemically modified and composite materials of chitin and chitosan derivatives for biomedical applications, such as tissue engineering, nanomedicine, drug delivery, and gene delivery.
Preface 5
Contents 8
About the Editors 10
1: Chitosan and Its Derivatives: A New Versatile Biopolymer for Various Applications 12
1.1 Chitin and Chitosan: General Characterization 13
1.2 Sources and Extraction of Chitosan from Raw Materials 14
1.3 Structure and Properties of Chitosan 16
1.4 Factors Affecting Physicochemical Properties of Chitosan 17
1.4.1 pH 17
1.4.2 Ionic Strength 18
1.4.3 Concentration 19
1.4.4 Molecular Weight 19
1.4.5 Degree of Deacetylation 20
1.4.6 Temperature 20
1.5 Modification of Chitosan 21
1.5.1 Physical Modification 21
1.5.2 Chemical Modification 22
1.5.3 Molecular Imprinting of Chitosan 25
1.6 Computational Modeling for Rational Designing of MIP and Chitosan-Based Material 26
1.7 Application 29
1.7.1 Biomedical Application 29
1.7.1.1 Biosensor 29
1.7.1.2 Cancer Diagnosis 29
1.7.1.3 Tissue Engineering 30
1.7.1.4 Wound Dressing 32
1.7.1.5 Drug Carrier 33
1.7.1.6 Antimicrobial Activity 34
1.7.2 Industrial Applications 36
1.7.2.1 Cosmetics 36
1.7.2.2 Paper Industry 36
1.7.2.3 Textile Industry 37
1.7.2.4 Solid-State Batteries 37
1.7.2.5 Agriculture 37
1.7.2.6 Food Processing 38
1.7.3 Environmental Applications 38
1.7.3.1 Flocculating Agent 38
1.7.3.2 Chelating Agent and Heave Metal Ion Trapper 41
1.7.3.3 Removal of Organic Pollutants 42
1.8 Conclusion 43
References 44
2: Application of Chitosan in Oral Drug Delivery 54
2.1 Introduction 55
2.2 Oral Drug Delivery 55
2.3 Chitosan as an Ideal Carrier for Oral Drug Delivery 56
2.4 Chitosan Tablets 57
2.5 Chitosan Capsules 58
2.6 Chitosan Beads and Granules 59
2.7 Chitosan Oral Gene Delivery 61
2.8 Chitosan Oral Peptide/Protein Delivery 65
2.9 Chitosan Nanoparticles 66
2.9.1 Quaternized Derivatives of Chitosan 66
2.9.2 Thiolated Chitosan 67
2.9.3 PEGylated Chitosan 69
2.10 Chitosan Films in Oral Drug Delivery Systems 69
2.11 Hydrogel Drug Delivery Systems 71
2.12 Chitosan Hydrogels 72
2.12.1 Physically Associated Chitosan Hydrogels 72
2.12.2 Chitosan Hydrogels Formed by Polyelectrolyte Complexes (PEC) 73
2.12.3 Chitosan-Alginate Hydrogels 73
2.12.4 Chitosan-Pectin Hydrogels 74
2.12.5 Chitosan-Carrageenan Hydrogels 74
2.12.6 Chitosan-Collagen Hydrogels 75
2.12.7 Cross-Linked Chitosan Hydrogels 75
2.13 Chitosan Hydrogels in Oral Drug Delivery Systems 76
2.13.1 Chitosan Hydrogels in Oral Cavity 76
2.13.2 Chitosan Hydrogels in GI Tract 77
2.14 Conclusion 78
References 78
3: Transdermal Delivery of Chitosan-Based Systems 85
3.1 Introduction 86
3.2 Transdermal Drug Delivery System (TDDS) 86
3.2.1 Advantages of Transdermal Drug Delivery Systems (TDDSs) 87
3.2.2 Disadvantages of Transdermal Drug Delivery System (TDDS) 87
3.3 Skin 88
3.3.1 Skin Structure 88
3.3.2 Skin Barrier Properties 90
3.3.3 The Barrier Property of Stratum Corneum (SC) 90
3.3.3.1 Skin Turnover as a Barrier 91
3.3.3.2 Transportation of Exogenous Substances from Stratum Corneum 91
3.3.3.3 Acidic Nature of Stratum Corneum 91
3.4 Overcoming the Barrier of Transdermal Delivery 92
3.4.1 Passive Methods 92
3.4.2 Active Methods 92
3.5 Skin Permeability Enhancement by Active Methods 93
3.5.1 Electrical Method 93
3.5.1.1 Iontophoresis 93
3.5.1.2 Electroporation 93
3.5.2 Mechanical Methods for Transdermal Delivery 94
3.5.2.1 Microneedle-Based Delivery 94
3.5.2.2 Skin Abrasion Method 94
3.5.2.3 Skin Perforation Technique 95
3.5.2.4 Needleless Injection 95
3.5.2.5 Suction Ablation Techniques 95
3.5.2.6 Skin Stretching Techniques 96
3.5.2.7 Ultrasound (Sonophoresis and Phonophoresis) 96
3.5.2.8 Laser Radiation and Photomechanical Waves 96
3.5.2.9 Magnetophoresis 97
3.5.2.10 Thermophoresis 97
3.5.2.11 Radio Frequency 97
3.6 Chitosan 98
3.6.1 Physicochemical Properties of Chitosan 99
3.6.2 Isolation of Chitosan 99
3.6.3 Chitosan Derivatives 100
3.6.3.1 Physical Modification of Chitosan 101
3.6.3.2 Chemical Modification of Chitosan 101
3.6.4 Therapeutic Properties of Chitosan 102
3.7 Important Properties of Chitosan 103
3.7.1 Controlled Drug Release 103
3.7.2 Mucoadhesive Properties 103
3.7.3 In Situ Gelling Properties 104
3.7.4 Transfection Enhancing Properties 104
3.7.5 Permeation Enhancing Properties 104
3.8 Transdermal Application of Chitosan 105
3.8.1 Penetration Mechanism of Chitosan Through Transdermal Route 105
3.8.2 Drug Release from Chitosan Nanoparticles 106
3.9 Chitosan-Based Formulations for Transdermal Delivery 107
3.9.1 Trimethylated Chitosan Nanoparticles 107
3.9.2 Chitosan/Cyclodextrin (CS/CD) Nanoparticles 108
3.9.3 Chitosan-Based Hydrogels for Transdermal Delivery 109
3.9.4 Chitosan Nanoparticles 109
3.9.5 Chitosan Nanocapsules 110
3.10 Conclusion 111
References 112
4: Chitosan-Based Ocular Drug Delivery Systems 117
4.1 Introduction 119
4.2 Major Ocular Diseases 120
4.3 Ocular Delivery Systems 121
4.4 Novel Ocular Delivery Systems 122
4.5 Intraocular Drug Transport Barriers 122
4.6 Ocular Transporters 123
4.7 Chitosan-Based Drug Delivery Systems 124
4.8 Chitosan-Based Responsive Drug Delivery System 124
4.8.1 Phase Separation 125
4.8.2 Covalent Cross Linking 130
4.9 Chitosan-Based Targeted Drug Delivery System (TDDS) 131
4.10 Chitosan-Based Gene Delivery System 135
4.11 Route of Administration of Gene Therapy 135
4.12 Vectors in Gene Therapy 136
4.13 Chitosan as Gene Therapy Vector 137
4.14 Conclusion 138
References 138
5: Functional Chitosan Carriers for Oral Colon-Specific Drug Delivery 145
5.1 Introduction 146
5.2 Chitosan 147
5.2.1 Physicochemical Properties 147
5.2.2 Biological Properties 149
5.3 Oral Colon-Specific Drug Delivery 150
5.3.1 Mode of Delivery 150
5.3.2 Limitations 150
5.4 Chitosan Derivatives/Formulations in Oral Colon-Specific Delivery 153
5.4.1 Design Features 153
5.4.2 Preparation Methods of Chitosan-Based Oral Colon-Specific Drug Delivery System 157
5.4.3 In Vitro and In Vivo Experimental Outcomes 158
5.4.4 Unique Characteristics and Limitations 161
5.5 Future Perspectives 161
5.6 Conclusion 165
References 166
6: Chitosan-Based Hydrogels for Drug Delivery 172
6.1 Introduction 173
6.2 Basic Concepts and Properties of Hydrogels 174
6.3 Strategies for Preparation of Hydrogels Based on Chitosan 176
6.3.1 Physical Crosslinking 176
6.3.2 Chemical Crosslinking 178
6.3.3 Interpenetrating and Semi-Interpenetrating Polymer Networks 180
6.4 Drug-Loading Techniques 180
6.5 Chitosan Hydrogels for Drug Delivery Application 183
6.6 Mechanisms of Drug Release 186
6.7 Conclusion and Future Prospects 190
References 190
7: Recent Advances in Chitosan-Based Systems for Delivery of Anticancer Drugs 200
7.1 Introduction 201
7.1.1 Cancer and Anticancer Drugs 201
7.1.1.1 Cancer 201
7.1.1.2 Some Common Anticancer Drugs 202
7.1.2 Problems Associated in Using Anticancer Drugs 206
7.1.3 Common Drug Carrier Systems for Anticancer Drugs 207
7.2 Chitosan as an Anticancer Drug Carrier 211
7.2.1 Characteristic Properties of Chitosan 211
7.2.2 Preparation of Drug-Loaded Chitosan Nanoparticles 214
7.2.3 Characterization of Chitosan Nanoparticles 219
7.3 Modification of Chitosan Nanoparticles for Anticancer Therapies 222
7.4 Drug Release Studies with Chitosan Nanoparticles 226
References 228
8: Chitosan-Based Systems for Gene Delivery 238
8.1 Introduction 239
8.1.1 Introduction to Gene Therapy 239
8.1.2 Various Gene Delivery Systems and Methods 239
8.1.3 Viral Vectors vs Non-viral Vectors for Gene Therapy 240
8.2 Chitosan for Gene Delivery 245
8.2.1 Physicochemical Properties of Chitosan 245
8.2.2 Modifications of Chitosan 246
8.2.3 Mechanism of Chitosan-Based Gene Delivery Systems 247
8.2.4 Biocompatibility, Biodegradability, and Stability of Chitosan-Based Systems 248
8.3 Chitosan-Based Gene Delivery Systems 250
8.3.1 Chitosan-Based Nanoparticles 250
8.3.2 Chitosan-Based DNA Vaccines 253
8.4 Challenges Associated with Chitosan-Based Gene Delivery Systems 253
8.4.1 Factors Affecting Chitosan as a Gene Delivery Vector 253
8.4.2 Limitations of Chitosan-Based Gene Delivery Systems 255
8.4.3 Comparison of Chitosan with Other Gene Delivery Systems 256
8.5 Commercial and Investigational Applications of Chitosan-Based Gene Therapy 258
8.6 Conclusions and Future Perspectives 262
References 262
9: Chitosan-Based Interpenetrating Polymer Networks: Drug Delivery Application 277
9.1 Introduction 278
9.2 Classification of IPNs 279
9.3 Advancement of Chitosan as IPN Component 279
9.4 Chitosan-Based IPNs as Drug Delivery Systems 280
9.4.1 Hydrogel 281
9.4.2 Microspheres/Microcomposites 287
9.4.3 Films 292
9.5 Conclusions and Perspectives 294
References 297
10: Chitosan-Based Systems in Tissue Engineering 304
10.1 Introduction 305
10.2 Chitosan: Structure and Extraction 306
10.3 Bone Tissue Engineering 308
10.3.1 Chitosan-Synthetic Polymer Hybrid Scaffolds 309
10.3.2 Chitosan-Calcium Phosphate Hybrid Scaffolds 310
10.3.3 Chitosan-Bioactive Glass Hybrid Scaffolds 311
10.3.4 Chitosan-Hydroxyapatite Hybrid Scaffolds 312
10.4 Cartilage Tissue Engineering 313
10.4.1 Chitosan-Based Fibrous Scaffolds 314
10.4.2 Chitosan-Based Scaffolds 316
10.4.3 Chitosan-Based Composite Scaffolds 317
10.5 Liver Tissue Engineering 318
10.5.1 Chitosan-Collagen Matrices 319
10.5.2 Chitosan-Based Microfibers 319
10.6 Nerve Tissue Engineering 319
10.6.1 Chitosan-Based Membranes 319
10.6.2 Chitosan-Based Hydrogels 320
10.7 Musculoskeletal Tissue Engineering 320
10.8 Conclusion 321
References 322
11: Chitosan-Based Nanoformulation as Carriers of Small Molecules for Tissue Regeneration 328
11.1 The Growth of Nanoformulations 328
11.2 Nanoformulations Based on Biomolecules 329
11.2.1 Biomolecule-Based Therapies 330
11.2.2 Biomolecules as Target Specificity Providers 330
11.3 Chitosan-Based Drug Delivery Systems 330
11.4 Small Molecules for Regenerative Medicine 331
11.5 An Insight into the Challenges of Tissue Engineering 332
11.5.1 The Need for Tissue Engineering 332
11.5.2 Engineered Scaffolds 333
11.5.3 Three-Dimensional Scaffolds 333
11.5.4 Material Modification of Scaffolds 334
11.5.5 Hydrogels of Chitosan 335
11.5.6 Incorporation of Growth Factors in Hydrogels 336
11.5.7 Chitosan-Based Wound Healing Materials 336
11.6 Small Molecules Entrapped Chitosan-Based Matrices for Tissue Regeneration 337
11.7 Nano-Based Chitosan Platforms for Tissue Regeneration 338
11.7.1 Integration of Metal/Metal Oxide to Chitosan Matrices 339
11.7.2 Chitosan-Carbon-Based Nanomaterial Scaffolds 339
11.8 Current Challenges in the Use of Chitosan-Based Matrix 340
11.9 Future Role of Chitosan in Tissue Regeneration 341
11.9.1 3D Printed Scaffolds 341
References 343
12: Chitosan-Based Systems for Theranostic Applications 350
12.1 Theranostics: A Novel Approach to Combine Diagnosis, Treatment, and Subsequent Imaging 351
12.1.1 Concerns for Theranostic Systems 351
12.1.2 Materials Used in Theranostic Applications 353
12.1.2.1 Iron Oxide Nanoparticles 353
12.1.2.2 Gold Nanoparticles (AuNPs) 353
12.1.2.3 Quantum Dots (QDs) 354
12.1.2.4 Carbon Nanotubes (CNTs) 354
12.1.2.5 Mesoporous Silica Nanoparticles (MSNs) 355
12.1.2.6 Lipid-Based Nanoparticle Platform: Liposomes, Solid Lipid Nanoparticles (SLNs), and Nanostructured Lipid Carriers (NL... 355
12.1.2.7 Dendrimers 356
12.2 Chitosan: A Programmable Polymer for Theranostic Applications 356
12.2.1 Advantages of Chitosan 356
12.2.2 Chitosan Structure and Properties 358
12.2.2.1 Chitosan Structure 358
12.2.2.2 Deacetylation/Acetylation Degree of Chitosan and Molecular Weight 359
12.2.2.3 Chitosan Solubility 359
12.2.2.4 Chitosan Properties 360
12.2.3 Chitosan Modification for Theranostics 363
12.2.4 Types of Chitosan-Based Systems for Theranostic Applications 368
12.2.4.1 Self-Assembled Nanoparticles 368
12.2.4.2 Cross-Linked Chitosan-Based Nanoparticles 369
12.2.4.3 Chitosan-Based Nanocapsules 371
12.3 Chitosan in Clinical Applications: Key Challenges 372
12.3.1 Drug Delivery, Bioimaging, and Hyperthermia 372
12.3.2 Chitosan in Bioresponsive Tissue-Engineered Scaffolds 373
12.3.3 Bio-sensing Applications 377
12.4 Conclusions and Future Perspective 380
References 381
13: Grafted Chitosan Systems for Biomedical Applications 392
13.1 Introduction 393
13.2 Synthesis of Grafted Chitosan 396
13.2.1 Grafting by Schiff Base Formation and Reductive Amination 398
13.2.2 Grafting by Amide Formation 398
13.2.3 Grafting by Click Reactions 399
13.2.4 Grafting by Nucleophilic Substitution Reaction 399
13.2.5 Grafting by Photoinitiation 399
13.2.6 Grafting Under Microwave Irradiation 399
13.2.7 Grafting by Cross-Linking Reaction 400
13.3 Properties of Grafted Chitosan 400
13.4 Nanocomposites of Grafted Chitosan 401
13.5 Antimicrobial Properties of Grafted Chitosan 401
13.6 Grafted Chitosan for Tissue Engineering and Regeneration 402
13.7 Grafted Chitosan in DNA and Gene Therapy 404
13.8 Anticancer Activity and Release Mechanism of Drug and Protein 407
13.9 Biosensor Applications of Grafted Chitosan 410
13.10 Other Applications of Grafted Chitosan 411
13.11 Summary and Conclusion 412
References 413
14: Chitosan-Based Systems for Controlled Delivery of Antimicrobial Peptides for Biomedical Application 421
14.1 Introduction 423
14.2 Challenges of Topical Microbial Infections 424
14.3 Chitosan as an Antimicrobial Agent 425
14.3.1 In Vitro and In Vivo Antimicrobial Activity of Chitosan 427
14.3.2 Antibacterial Mechanism of Action of Chitosan 430
14.4 Antimicrobial Peptides (AMPs) as Antimicrobial Agents 433
14.4.1 Classification of AMPs 433
14.4.2 Mechanisms of Action of AMP 439
14.4.3 Resistance to AMPs 439
14.4.4 AMPs: Activity Versus Toxicity Balance 441
14.4.5 Clinical Applications of AMPs 441
14.5 AMP-Chitosan Combination and Potential Synergies as Carriers 442
14.5.1 Chemical Modification of Chitosan Polymer 442
14.5.2 Chemical Coupling of Chitosan with AMPs 447
14.5.2.1 Chitosan-Anoplin 447
14.5.2.2 Chitosan-hLF-1-11 448
14.5.2.3 Chitosan-Nisin 448
14.5.2.4 Chitosan-Dhvar-5 449
14.5.2.5 Chitosan-HHC10 449
14.5.2.6 Chitosan-KLAK-PEG-GPLGVRGC 449
14.5.3 Chitosan as Carrier for AMPs 450
14.5.3.1 Chitosan-AMP-Based NPs 450
14.5.3.2 Chitosan-AMP-Based Membrane 451
14.6 Conclusions and Perspectives 451
References 452
15: Antibacterial Activity of Chitosan-Based Systems 462
15.1 Introduction 462
15.2 Antibacterial Materials 463
15.2.1 Antibacterial Activity of Chitosan-Based System 464
15.2.2 History 465
15.2.3 Sources of Chitosan 465
15.2.4 Water Soluble 466
15.2.5 Derivatives of Chitosan 466
15.2.6 Degree of Deacetylation 466
15.3 Mechanism of Antibacterial Activity 467
15.4 Factors Affecting Antibacterial Property 468
15.4.1 Concentration of Chitosan 468
15.4.2 Molecular Weight 469
15.4.3 Positive Charge Density 470
15.4.4 Hydrophilic/Hydrophobic Characteristic 470
15.4.5 Chelating Capacity 471
15.4.6 pH 471
15.4.7 Ionic Strength 472
15.4.8 Physical State 472
15.4.8.1 Antimicrobial Activity in Soluble State 472
15.4.8.2 Antimicrobial Activity in Solid State 473
15.4.9 Temperature and Time 473
15.4.10 Microbial Factors 473
15.4.10.1 Microbial Species 473
15.4.10.2 Part of Microorganism 474
15.4.10.3 Cell Age 475
15.5 Complexes of Chitosan with Certain Materials 475
15.5.1 Antimicrobial Activity of Chitosan Nanoparticles Loaded with Antibiotics or Other Microbicidal Substances 476
15.5.2 Antimicrobial Activity of Chitosan/Metal Nanocomposites 477
15.5.3 Antimicrobial Activity of Chitosan Nanoparticles on Bacterial Biofilm 478
15.6 Applications of the Antimicrobial Activity of Chitosan-Based Nanosystems 478
15.6.1 Wound Healing 479
15.6.2 Textile and Fabrics 480
15.6.3 Food Packaging 480
15.6.4 Application in Medical Industry 481
15.6.5 Antibacterial Coating 482
15.7 Conclusions and Future Perspectives 489
References 490
| Erscheint lt. Verlag | 5.3.2020 |
|---|---|
| Zusatzinfo | XII, 489 p. 68 illus., 46 illus. in color. |
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Pflege |
| Medizin / Pharmazie ► Physiotherapie / Ergotherapie ► Orthopädie | |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Chemie ► Organische Chemie | |
| Technik ► Maschinenbau | |
| Technik ► Medizintechnik | |
| Technik ► Umwelttechnik / Biotechnologie | |
| Wirtschaft | |
| Schlagworte | Chitosan Hydrogel • Drug Delivery • Gene Delivery • Theranostic Application • Tissue engineering |
| ISBN-10 | 981-15-0263-3 / 9811502633 |
| ISBN-13 | 978-981-15-0263-7 / 9789811502637 |
| Haben Sie eine Frage zum Produkt? |
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