Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids

2334_fm.pdf......Page 1
Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids......Page 2
Dedication......Page 4
Preface......Page 5
About the Editor......Page 6
Contributors......Page 7
Contents......Page 12
CONTENTS......Page 28
Table of Contents......Page 0
1.1 INTRODUCTION......Page 29
1.2.1.2 Poly(phosphoester)s......Page 34
1.2.1.4 Polyesters......Page 35
1.2.1.6 Polycarbonates......Page 36
1.2.2.1 Silicone Elastomers......Page 37
1.2.2.4 Poly(ethylene oxide)/Poly(ethylene glycol)......Page 38
1.3.1.1 Chitin and Chitosan......Page 39
1.3.3 COLLAGEN......Page 40
1.4 GENETICALLY ENGINEERED AND HYBRID BIOMATERIALS......Page 41
1.4.3 SILK ELASTIN-LIKE BLOCK COPOLYMERS......Page 42
1.5.1.1 Differential Scanning Calorimetry......Page 43
1.5.1.2 THERMOGRAVIMETRIC ANALYSIS (TGA)......Page 44
1.5.2.1 Osmometry......Page 45
1.5.2.2 Dynamic Light Scattering......Page 47
1.5.2.4 Gel Permeation Chromatography......Page 48
1.5.3.1 Determination of Stereochemical Configurations......Page 50
1.5.3.2 Two-Dimensional NMR......Page 51
1.5.4.1 Transmission Electron Microscopy/Scanning Electron Microscopy......Page 52
1.5.4.2 Atomic Force Microscopy......Page 53
1.5.5.2 Infrared Spectroscopy......Page 54
1.5.5.4 Near Infrared Spectroscopy......Page 55
1.5.5.5 MASS SPECTROSCOPY......Page 56
1.5.5.6 Electrospray Mass Spectrometry......Page 57
1.5.5.7 MALDI-TOF Mass Spectrometry......Page 58
1.5.5.8 X-ray Photoelectron Spectroscopy......Page 59
1.5.6 GEL ELECTROPHORESIS......Page 61
1.7 ABBREVIATIONS......Page 62
REFERENCES......Page 63
CONTENTS......Page 73
2.1 INTRODUCTION......Page 74
2.2.1 MECHANISM AND KINETICS......Page 75
2.2.2.3 Polyamides......Page 78
2.2.2.4 Polyimides......Page 79
2.2.2.5 Polyethers......Page 80
2.3.1 FREE-RADICAL CHAIN GROWTH POLYMERIZATION......Page 81
2.3.1.1 Kinetics......Page 84
2.3.2.1 Kinetics......Page 86
2.3.2.4.1 Polyisobutylene......Page 89
2.4 RING-OPENING POLYMERIZATION......Page 90
2.4.1.1 Kinetics......Page 92
2.4.3.1 Enzyme-Catalyzed Ring-Opening Polymerization......Page 93
2.5 DENDRITIC POLYMERS......Page 95
REFERENCES......Page 98
3.1 INTRODUCTION......Page 99
3.2.1 GENERAL PROPERTIES OF COPOLYMERS......Page 101
3.2.2 PHARMACEUTICAL APPLICATIONS OF COPOLYMERS......Page 102
3.3.1 GENERAL PROPERTIES OF BLOCK COPOLYMERS......Page 104
3.3.2 THERMOPLASTIC ELASTOMERIC BLOCK COPOLYMERS......Page 105
3.3.3 PHARMACEUTICAL APPLICATIONS OF BLOCK COPOLYMERS......Page 107
3.4.1 GENERAL PROPERTIES OF STIMULI-SENSITIVE POLYMERS......Page 109
3.4.2 THERMOSENSITIVE POLYMERS......Page 110
3.4.3 OTHER STIMULI-SENSITIVE POLYMERS......Page 112
3.4.4 APPLICATIONS OF STIMULI-SENSITIVE POLYMERS......Page 113
3.5 CONCLUDING REMARKS......Page 114
REFERENCES......Page 115
4.1 INTRODUCTION......Page 120
4.2.1 VISCOSITY MEASUREMENTS......Page 121
4.2.2 LIGHT SCATTERING MEASUREMENTS......Page 123
4.3.1 CHEMISTRY AND CHARACTERIZATION......Page 124
4.3.2 PHARMACEUTICAL APPLICATIONS OF BRANCHED POLYMERS......Page 126
4.4.1 CHEMISTRY AND CHARACTERIZATION......Page 127
4.4.2 PHARMACEUTICAL APPLICATIONS......Page 129
4.5.1 CHEMISTRY AND CHARACTERIZATION......Page 130
4.5.2 PHARMACEUTICAL APPLICATIONS OF DENDRIMERS......Page 132
4.6.1 NETWORK FORMATION OF MULTIFUNCTIONAL PRECURSORS......Page 135
ACKNOWLEDGMENT......Page 138
REFERENCES......Page 139
CONTENTS......Page 144
5.1 INTRODUCTION......Page 145
5.2.1 PHYSICAL, CHEMICAL, AND BIOLOGICAL PROPERTIES OF PEG......Page 146
5.2.2 PROPERTIES OF PEG-PROTEIN CONJUGATES......Page 148
5.3.2 REACTIVITY OF PROTEIN FUNCTIONAL GROUPS......Page 151
5.4 PEG REAGENTS FOR CONJUGATION OR CROSS-LINKING......Page 154
5.4.1 PEG STRUCTURES......Page 155
5.4.2.1.1 PEGs for Carboxyl Modification......Page 157
5.4.2.2.1 Acylating PEGs for Amine Modification......Page 158
5.4.2.2.2 Alkylating PEGs for Amine Modification......Page 163
5.4.2.3 PEGs for Cysteine Modification......Page 166
5.4.2.5 PEGs for Reversible Modification......Page 168
5.4.2.6 Heterobifunctional PEGs for Tethering, Cross-Linking, and Conjugation......Page 170
5.5.1 GENERAL CONSIDERATION FOR PROTEINS AND PEPTIDES......Page 173
5.5.2 NONSPECIFIC MODIFICATION......Page 176
5.5.3 SELECTIVE MODIFICATION......Page 178
5.6.1 PURIFICATION......Page 181
5.6.2.1 Degree of Substitution......Page 184
5.6.2.2 Site of Substitution......Page 187
5.6.2.3 Molecular Weight/Molecular Size......Page 190
5.6.2.4 Conformational Analysis......Page 191
5.6.2.5 Quantification of PEG-Proteins in Biological Samples......Page 192
5.7 CLINICAL APPLICATION OF PEG-MODIFIED PROTEINS......Page 193
5.8 CONCLUSIONS......Page 196
REFERENCES......Page 197
CONTENTS......Page 211
6.2 THE COMPLEMENT SYSTEM......Page 212
6.2.1 ACTIVATION PATHWAYS......Page 213
6.2.1.1 The Classical Complement Pathway......Page 214
6.2.1.3 The Alternative Complement Pathway......Page 215
6.2.2 THE MEMBRANE ATTACK COMPLEX......Page 217
6.2.3.1 Cellular Interaction......Page 218
6.2.4 COMPLEMENT SYSTEM AND BIOMATERIALS......Page 219
6.2.4.1 Dextran and its Derivatives......Page 221
6.2.4.2 Heparin and its Derivatives......Page 222
6.3 INJECTABLE COLLOIDAL DRUG CARRIERS......Page 224
6.3.1.1 Capture by Mononuclear Phagocytic System......Page 225
6.3.1.2 Extravasation through Blood Vessel Endothelium......Page 226
6.3.2 SYSTEMS AVOIDING UPTAKE BY PHAGOCYTIC CELLS......Page 228
6.3.2.1.1 Protein–Surface Interactions in the Presence of Poly(ethylene glycol)......Page 229
6.3.2.1.2 Protein–Particle Interactions in the Presence of Poly(ethylene glycol)......Page 231
6.3.2.1.3 Fate of Polymer-Coated Long-Circulating Colloidal Drug Carriers......Page 232
6.3.2.2.1 The Use of Different Natural Compounds......Page 233
6.3.2.2.2 The Use of Dextran......Page 234
6.3.2.3 Targeting Systems......Page 235
6.4.1 AN EXAMPLE OF COMPLEMENT ACTIVATION ASSAY: THE CH50 TEST......Page 236
6.4.2 INTERACTION WITH COLLOIDAL DRUG CARRIERS......Page 238
6.4.2.1 Liposomes......Page 239
6.4.2.2.1 PEGylated Polymeric Particles......Page 241
6.4.2.2.2 Biomimetic Particles......Page 242
6.4.3 CONSEQUENCES OF COMPLEMENT ACTIVATION......Page 243
6.5 CONCLUSION......Page 244
REFERENCES......Page 245
CONTENTS......Page 255
7.2.1 LIPID BILAYER......Page 256
7.2.2 LIPID RAFTS......Page 258
7.3.1 EPITHELIAL BARRIERS......Page 259
7.3.2 ANCHORING JUNCTIONS......Page 260
7.3.3 OCCLUDENS JUNCTIONS......Page 261
7.3.4 ENDOTHELIAL BARRIERS......Page 264
7.4.1 MEMBRANE PERMEABILITY AND PASSIVE DIFFUSION......Page 265
7.4.2 FACILITATED PASSIVE DIFFUSION......Page 267
7.4.3 ACTIVE CARRIER-MEDIATED TRANSPORTERS......Page 268
7.4.4 NUCLEOSIDE TRANSPORTERS......Page 269
7.4.5 PEPTIDE TRANSPORTERS......Page 270
7.4.6 AMINO ACID TRANSPORTERS......Page 272
7.4.7 EFFLUX TRANSPORTERS......Page 274
7.4.9 NUCLEAR MEMBRANE TRANSPORT......Page 277
7.5 VESICULAR TRANSPORT......Page 279
7.5.2 CLATHRIN-MEDIATED ENDOCYTOSIS......Page 281
7.5.3 TARGETING AND FUSION OF VESICLES......Page 284
7.5.4 ENDOSOMES AND INTRACELLULAR VESICLES......Page 286
7.5.5 ENDOSOMES AND THE CYTOSKELETON......Page 287
7.6.1 NUCLEASES......Page 288
7.6.2 PEPTIDASES......Page 289
7.7.2 ORAL......Page 291
7.7.3 LUNG......Page 292
7.7.4 NASAL......Page 293
7.7.5 SKIN......Page 295
7.8 CONCLUDING REMARKS......Page 296
REFERENCES......Page 297
8.1 INTRODUCTION......Page 299
8.2 PHARMACOKINETICS OF PROTEINS......Page 300
8.2.1 PROTEIN ABSORPTION......Page 301
8.2.2 PROTEIN DISTRIBUTION......Page 303
8.2.3.2 Gastrointestinal Protein Metabolism......Page 305
8.2.3.3 Renal Protein Metabolism......Page 306
8.2.3.5 Receptor-Mediated Protein Metabolism......Page 307
8.2.4 IMMUNOGENICITY AND PROTEIN PHARMACOKINETICS......Page 308
8.3.2 OLIGONUCLEOTIDE DISTRIBUTION......Page 310
8.3.4 SECOND GENERATION PHOSPHOROTHIOATE OLIGONUCLEOTIDES......Page 312
8.5 CONCLUDING REMARKS......Page 313
REFERENCES......Page 314
9.1 INTRODUCTION......Page 319
9.2 BIODISTRIBUTION OF NUCLEIC ACIDS......Page 321
9.3.1 CIRCULATION IN THE BLOODSTREAM......Page 322
9.3.2 EXTRAVASATION......Page 325
9.3.3 OPSONIZATION AND CLEARANCE BY RES......Page 326
9.3.4 ORGAN DISTRIBUTION......Page 327
9.4 LOCAL APPLICATION OF POLYPLEXES......Page 329
9.4.1 INTRATRACHEAL AND AEROSOL ADMINISTRATION......Page 330
9.4.3 INTRATUMORAL INJECTION......Page 331
9.5 STRATEGIES TO INCREASE EFFICIENCY OF POLYPLEXES......Page 332
9.5.1.1 PEGylation......Page 333
9.5.1.3 Modification of Polyplexes with Pluronic......Page 335
9.5.2.1 Passive Targeting......Page 336
9.5.2.2 Active Targeting......Page 337
REFERENCES......Page 338
10.1 INTRODUCTION......Page 346
10.2 SUBCELLULAR TRAFFICKING OF MACROMOLECULES......Page 347
10.3 EXPERIMENTAL METHODS......Page 351
10.4.1 POLYMER CONJUGATES......Page 352
10.4.2 NANO-/MICROPARTICLES......Page 355
10.4.3 POLYPLEXES......Page 359
10.5 CONCLUDING REMARKS......Page 365
REFERENCES......Page 366
CONTENTS......Page 374
11.2 STABILITY OF PROTEINS......Page 375
11.2.1 CHEMICAL DEGRADATION OF PROTEINS......Page 376
11.2.1.1 Hydrolysis......Page 377
11.2.1.3 Oxidation......Page 378
11.2.1.6 Degradation at Cystinyl Residues......Page 379
11.2.2 PHYSICAL DEGRADATION OF PROTEINS......Page 381
11.2.2.3 Effect of Salts......Page 382
11.3 PROTEIN STABILIZATION......Page 383
11.4.1 DEGRADATION OF RNA......Page 384
11.4.2.1 Hydrolysis of DNA......Page 388
11.4.2.3 Oxidation of DNA......Page 391
11.4.3 PHYSICAL STABILITY OF NUCLEIC ACIDS......Page 395
11.6 CONCLUDING REMARKS......Page 396
REFERENCES......Page 397
CONTENTS......Page 399
12.1 INTRODUCTION......Page 400
12.2.1 FORMULATIONS FOR PARENTERAL ADMINISTRATION......Page 401
12.2.2 NON-PARENTERAL ROUTES OF ADMINISTRATION......Page 402
12.3.1 CHEMICAL MODIFICATION OF PROTEINS AND PEPTIDES......Page 403
12.3.1.1 Rapid-Acting Insulin Analogues......Page 404
12.3.1.3 PEGylation of Proteins......Page 405
12.3.2 PROTEIN AND PEPTIDE DELIVERY SYSTEMS......Page 406
12.4.1 CHEMICAL DEGRADATION OF PROTEINS AND PEPTIDES......Page 407
12.4.2 PHYSICAL STABILITY OF PROTEINS AND LARGER PEPTIDES......Page 410
12.4.3 STRATEGIES FOR IMPROVING STABILITY......Page 412
12.4.4 IMMUNOGENICITY–A POTENTIAL RISK FACTOR......Page 413
12.5.1 ANALYSIS OF THE THREE-DIMENSIONAL PROTEIN STRUCTURE......Page 414
12.5.2 ANALYSIS OF PROTEIN DEGRADATION......Page 415
12.5.3 PROTEIN FORMULATION AND ANALYTICAL METHODOLOGY IN PRACTICE......Page 418
12.6 CONCLUDING REMARKS......Page 419
REFERENCES......Page 420
CONTENTS......Page 423
13.1 INTRODUCTION......Page 424
13.2.1.1 Emulsions......Page 425
13.2.1.2 W/O/W Emulsions......Page 427
13.2.1.3 W/O/O Emulsion-Phase Inversion......Page 430
13.2.2 COMPLEX COACERVATION......Page 431
13.2.3 THERMAL DENATURATION AND CROSSLINKING......Page 433
13.2.4 SPRAY-DRYING......Page 434
13.2.5 INTERFACIAL/MONOMER/EMULSION POLYMERIZATION......Page 436
13.3.1 ADSORPTION OF NUCLEIC ACID......Page 437
13.4 STRATEGIES TO ENHANCE CELLULAR UPTAKE......Page 438
13.5 STRATEGIES TO ENHANCE ENDOSOMAL RELEASE......Page 439
13.6 STRATEGIES TO CONTROL DNA RELEASE......Page 440
13.6.1 POLYMER HYDROPHOBICITY......Page 441
13.6.3 INCLUSION OF HYDROPHILIC AGENTS......Page 442
13.7.1 DNA VACCINES......Page 443
13.8 CONCLUDING REMARKS......Page 446
REFERENCES......Page 447
14.1 INTRODUCTION......Page 455
14.2 PEPTIDES AND PROTEINS AS DRUGS: ADVANTAGES AND ASSOCIATED PROBLEMS......Page 456
14.3 POSSIBLE SOLUTIONS: LIPOSOMES AS PHARMACEUTICAL CARRIERS......Page 459
14.4 LIPOSOMAL ENZYMES......Page 462
14.4.1 ENZYMES FOR TREATMENT OF LYSOSOMAL STORAGE DISEASES......Page 463
14.4.3 OTHER ENZYMES......Page 465
14.5.1 PROTEINS OTHER THAN ENZYMES......Page 467
14.5.2.1 Insulin......Page 468
14.5.2.2 Other Peptides: Cytokines......Page 469
14.6 LIPOSOMES AS PROTEIN AND PEPTIDE CARRIERS FOR IMMUNOLOGICAL APPLICATIONS......Page 470
REFERENCES......Page 472
CONTENTS......Page 482
15.1 INTRODUCTION......Page 483
15.2.3 SECONDARY OR ACQUIRED RESISTANCE......Page 484
15.2.7 NONPUMP RESISTANCE......Page 485
15.2.8.2 Development of Multidrug Resistance During Chronic Exposure to a Drug......Page 486
15.3.1 PREVENTION OF DRUG ENTRY......Page 488
15.3.2 ACTIVE EFFLUX OF DRUGS......Page 489
15.3.2.3 Proteins Involved in Multidrug Resistance in Human and Microorganisms......Page 490
15.3.4 ACTIVATION OF ANTIOXIDANT SYSTEMS......Page 495
15.3.4.1 Free Oxygen Radicals and Lipid Peroxidation......Page 496
15.3.4.2 Activation of Antioxidant Systems After Adaptation to Anticancer Drug......Page 497
15.3.5 DNA REPAIR, REPLICATION AND BIOSYNTHESIS......Page 498
15.3.6.2 BCL2 Protein Family......Page 499
15.3.6.3 Activation of Antiapoptotic Cellular Defense in Cancer Cells During the Treatment with Anticancer Drugs......Page 501
15.3.7 SUMMARY......Page 502
15.4.1 METHODS OF MODULATION OF MULTIDRUG RESISTANCE PHENOTYPE......Page 503
15.4.1.2 Biochemical Modulation......Page 504
15.4.1.3 Gene Therapy......Page 505
15.4.2.1 Enhanced Permeability and Retention (EPR) Effect......Page 506
15.4.2.2 Accumulation of Polymer-Bound Drugs in Solid Tumor......Page 507
15.4.3.2 Modulation of Pump Resistance......Page 508
15.4.3.4 Modulation of Nonpump Resistance......Page 509
15.5 CONCLUSIONS......Page 510
REFERENCES......Page 511
CONTENTS......Page 514
16.1 INTRODUCTION......Page 515
16.2.1 PATHWAYS TO CROSS INTESTINAL EPITHELIAL BARRIERS......Page 516
16.2.4.1 SLC Transporters......Page 517
16.2.4.2 ABC Transporters......Page 518
16.3.2 SUBSTRATE SELECTIVITY AND PH-DEPENDENCE OF PEPT1......Page 519
16.3.3 INTESTINAL REGIONAL DIFFERENCE OF ABSORPTION OF PEPT1 SUBSTRATES......Page 523
16.4.1 SELECTION OF BIOMATERIALS TO MAINTAIN LOWER PH IN INTESTINAL LUMEN......Page 524
16.4.2 SELECTION OF TEST COMPOUND FOR PEPT1-MEDIATED ABSORPTION......Page 525
16.4.3 IMPROVEMENT OF INTESTINAL ABSORPTION OF CEFIXIME BY EUDRAGIT L100-55......Page 527
16.5 CONCLUDING REMARKS......Page 530
REFERENCES......Page 531
17.1 INTRODUCTION......Page 533
17.2 PTDs DERIVED FROM NATURALLY OCCURRING PROTEINS......Page 534
17.2.1 HIV-1/ TAT PROTEIN......Page 535
17.2.2 HOMEOBOX PROTEINS......Page 539
17.2.4 OTHER PTD DERIVED FROM NATURALLY OCCURRING PROTEINS......Page 541
17.4 PROTEIN TRANSDUCTION DOMAINS FOR DELIVERY OF NUCLEIC ACIDS......Page 542
17.4.1 DELIVERY OF DNA......Page 543
17.5 CONCLUDING REMARKS......Page 544
REFERENCES......Page 545
CONTENTS......Page 550
18.1 INTRODUCTION......Page 551
18.2 NUCLEIC ACIDS......Page 552
18.2.1.1 Double Stranded Nucleic Acids......Page 554
18.2.1.2 Single Stranded Nucleic Acids......Page 556
18.3.1.1 RNase H Mediated mRNA Degradation......Page 557
18.3.1.3 Antisense Modulation of mRNA Splicing......Page 558
18.3.2 CHEMISTRY......Page 559
18.3.2.2 Phosphorothioates......Page 560
18.3.2.4 Peptide Nucleic Acids......Page 561
18.3.3 APPLICATIONS......Page 562
18.4.1 MECHANISM......Page 563
18.5 CATALYTIC NUCLEIC ACIDS......Page 564
18.5.1.1 Trans-Cleaving Ribozymes......Page 565
18.5.1.2 Trans-Splicing Ribozymes......Page 566
18.5.3 DNAZYMES......Page 567
18.6 APTAMERS......Page 568
18.6.1 MECHANISM......Page 569
18.6.2 CHEMISTRY......Page 570
18.6.4 APPLICATIONS......Page 571
18.7.1 TRIPLEX FORMATION......Page 572
18.7.2.2 Genome Modification......Page 574
18.8.1 RNAI MECHANISM......Page 575
18.8.2 SIRNA CHARACTERISTICS......Page 577
18.8.4 RNAI PLASMID VECTORS......Page 578
18.9 CONCLUSIONS......Page 579
REFERENCES......Page 580
CONTENTS......Page 587
19.1 INTRODUCTION......Page 588
19.2.1 FIRST-GENERATION OLIGONUCLEOTIDES......Page 589
19.2.2 SECOND- AND THIRD-GENERATION OLIGONUCLEOTIDES......Page 591
19.2.3 MORPHOLINO OLIGOMERS......Page 593
19.3 MECHANISMS OF ACTION OF ANTISENSE OLIGONUCLEOTIDES......Page 595
19.4 CpG MOTIFS AND IMMUNOSTIMULATION......Page 597
19.5 TRIPLEX FORMING OLIGONUCLEOTIDES (TFOs)......Page 598
19.6.2 STRATEGIES TO IMPROVE TRIPLEX DNA STABILITY......Page 600
19.7 INHIBITION OF TRANSCRIPTION BY TRIPLEX FORMATION......Page 601
19.8 PHARMACOKINETICS OF OLIGONUCLEOTIDES......Page 602
19.9 CELLULAR UPTAKE OF OLIGONUCLEOTIDES......Page 604
19.10 DELIVERY STRATEGIES OF OLIGONUCLEOTIDES......Page 606
19.10.1 CONJUGATION OF LIPOPHILIC MOLECULES......Page 607
19.10.3 PEGYLATION OF OLIGONUCLEOTIDES......Page 609
19.10.4 MULTIVALENT CARBOHYDRATE CLUSTERS......Page 610
ACKNOWLEDGMENT......Page 611
REFERENCES......Page 612
20.1 INTRODUCTION......Page 619
20.2 NUCLEIC ACID CHAPERONES......Page 620
20.3 DESIGN OF ARTIFICIAL MATERIALS FOR ENHANCING NUCLEIC ACID HYBRIDIZATION......Page 622
20.4 CHARACTERIZATION OF CATIONIC COMB-TYPE COPOLYMER AS A NUCLEIC ACID CHAPERONE......Page 624
20.5 DNA ANALYSIS USING CHAPERONING ACTIVITY OF PLL-g-Dex......Page 626
REFERENCES......Page 630
21.1 INTRODUCTION......Page 633
21.2.1 CONVENTIONAL PROMOTERS......Page 635
21.2.2.1 Liver-Specific Promoters......Page 636
21.2.2.2 Tumor-Specific Promoters......Page 637
21.2.2.4 Skeletal Muscle/Heart Muscle-Specific Promoters......Page 639
21.2.2.6 Lung-Specific Promoters......Page 640
21.2.2.8 Brain/Neuron-Specific Promoter......Page 641
21.2.2.9 Other Tissue-Specific Promoters......Page 642
21.2.3 INDUCIBLE PROMOTERS......Page 643
21.4 POLYADENYLATION SIGNAL......Page 645
21.6 TWO STEP TRANSCRIPTION AMPLIFICATION (TSTA) SYSTEM......Page 646
21.7 NUCLEAR TARGETING......Page 647
21.8 CpG DEPLETED PLASMID AND MINICIRCLE PLASMID......Page 648
REFERENCES......Page 649
22.1 INTRODUCTION......Page 661
22.2.1 STRUCTURE OF CATIONIC POLYMERS......Page 662
22.2.2 TYPES OF CHARGEABLE MOIETY......Page 663
22.2.3 EFFECT OF CHARGE DENSITY AND MOLECULAR WEIGHT......Page 664
22.2.4 DEGRADABILITY......Page 665
22.3.2 BIOCOMPATIBILITY ISSUES......Page 669
22.3.3 GRAFT OR SURFACE FUNCTIONALITY......Page 670
22.3.4 FABRICATION OF METAL SURFACE WITH CATIONIC MOIETY FOR DNA BINDING......Page 672
22.3.5 LIGANDS FOR TARGETING......Page 673
22.5 CONCLUDING REMARKS......Page 674
REFERENCES......Page 675