q 2006 by Taylor & Francis Group, LLC - Developers

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grateful to the wonderful people at Taylor & Francis-CRC Press, including Stephen Zollo, Patricia Roberson, and many others, who have made the concept of this book into reality. Any comments and constructive criticisms of the book can be sent to the editor at m.amiji@neu.edu. q 2006 by Taylor & Francis Group, LLC
Editor Dr. Mansoor M. Amiji received his undergraduate degree in pharmacy from Northeastern University in 1988 and his PhD in pharmaceutics from Purdue University in 1992. His areas of specialization include polymeric biomaterials, advanced drug delivery systems, and nanomedical technologies. Dr. Amiji’s research interests include the synthesis of novel polymeric materials for medical and pharmaceutical applications; surface modification of cationic polymers by the complexationinterpenetration method to develop biocompatible materials; the preparation and characterization of polymeric membranes and microcapsules with controlled permeability properties for medical and pharmaceutical applications; target-specific drug and vaccine delivery systems for gastrointestinal tract infections; localized delivery of cytotoxic and anti-angiogenic drugs for solid tumors in novel biodegradable polymeric nanoparticles; intracellular delivery systems for drugs and genes using target-specific, long-circulating, biodegradable polymeric nanoparticles; and gold and iron-gold core-shell nanoparticles for biosensing, imaging, and delivery applications. His research has received sustained funding from the National Institutes of Health (NIH), the National Science Foundation (NSF), foundations, and local industries. Dr. Amiji is Professor and Associate Chair of the Pharmaceutical Sciences Department and Co- Director of the Northeastern University Nanomedicine Education and Research Consortium (NERC). The NERC oversees a doctoral training grant in nanomedicine science and technology that was co-funded by the NIH and NSF. He has two published books, Applied Physical Pharmacy and Polymeric Gene Delivery: Principles and Applications, along with numerous manuscript publications. He has also received a number of awards, including the 2003 Eurand Award for Innovative Oral Drug Delivery Research, Third Prize. Dr. Amiji has supervised the research efforts of over 50 postdoctoral associates, doctoral and master’s level graduate students, and undergraduate honors students over the last 13 years. His teaching responsibilities include the Doctor of Pharmacy (PharmD) program and graduate programs (MS and PhD) in pharmaceutical sciences, biotechnology, and nanomedicine. q 2006 by Taylor & Francis Group, LLC
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Page 7 and 8: Foreword We are at the threshold of
Page 9: Preface With parallel breakthroughs
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Page 20 and 21: Chapter 10 Poly(L-Glutamic Acid): E
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Page 24 and 25: 4 Nanotechnology for Cancer Therapy
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40 Nanotechnology for Cancer Therap
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44 4.1 INTRODUCTION The recent deve
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46 (Gly-Phe-Leu-Gly) was developed.
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48 charged generation 5 PAMAM dendr
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50 Using a mannosylated cholesterol
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52 without any changes in the funct
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54 4.4.2.4 Folate Receptor-Mediated
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60 Targeting species Therapeutic 5.
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62 QD+NLS 70kD Dextran Merge QD+MLS
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64 (a) (b) Peptide Peptide Peptide
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66 (e.g., glycans, lipids, oligonuc
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68 layer-by-layer absorption of pol
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70 5.3 CHALLENGES IN INTEGRATING MU
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6 CONTENTS Neutron Capture Therapy
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Neutron Capture Therapy of Cancer 7
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106 7.5.1 Applicability of Standard
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108 consensus as to what measuremen
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110 a nanomaterial. AFM uses a nano
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112 In addition to size, the shape
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114 presence of all these entities
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116 concentration-dependent changes
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118 limits cellular uptake, resulti
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120 Nanotechnology for Cancer Thera
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124 been shown to cause liver injur
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128 7.5.2 IMMUNOGENICITY This issue
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8 CONTENTS Nanotechnology: Regulato
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TABLE 8.1 Nanomedicines: Drugs/Devi
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Regulatory Perspective in Nanotechn
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9 CONTENTS Polymeric Conjugates for
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Polymeric Conjugates for Angiogenes
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10 CONTENTS Poly(L-Glutamic Acid):
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Poly(L-Glutamic Acid): Efficient Ca
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202 development. For example, styre
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204 blood circulation time and pref
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206 11.3.2 MR IMAGING OF A PARAMAGN
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208 FIGURE 11.6 Coronal MR slice im
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210 strong enhancement in the heart
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216 Research in the past decade has
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218 While the majority of work on t
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220 12.4.2.1 Integrins as Targets f
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222 cytotoxicity. Consequently, enc
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224 are lectin-carbohydrate, ligand
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226 H1299 cells was significantly i
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13 CONTENTS Long-Circulating Polyme
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Long-Circulating Polymeric Nanopart
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14 CONTENTS Biodegradable PLGA/PLA
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Biodegradable PLGA/PLA Nanoparticle
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15 CONTENTS Poly(Alkyl Cyanoacrylat
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Poly(Alkyl Cyanoacrylate) Nanoparti
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16 CONTENTS Aptamers and Cancer Nan
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Aptamers and Cancer Nanotechnology
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318 17.5.3.2 Paclitaxel Formulation
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320 TABLE 17.1 Examples of Polymers
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322 are block copolymer vesicles th
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324 17.2.4 PROPERTIES OF MICELLE FO
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328 The amphiphilic or polar nature
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330 of paclitaxel-loaded micelles.
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332 of intracellular drug accumulat
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334 organelles, the non-ionic Pluro
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338 foreign bodies present within t
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340 PEG-b-PDLLA copolymers. Therefo
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342 For in vivo delivery, the LCST
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344 In cases where nuclear targetin
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18 PEO-Modified Poly(L-Amino Acid)
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PEO-Modified Poly(L-Amino Acid) Mic
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388 Hydrophilic block Single polyme
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390 concentrations, and organic sol
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392 micelles used for solubilizatio
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394 N O NH2 Nicotinamide Sodium nic
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396 hydrotropic moieties. The main
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TABLE 19.4 Modified Hydrotropic Mon
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402 The loading content of paclitax
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404 concentrations that are clinica
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410 bioavailability, certain clinic
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412 It has been shown that the EPR
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O 2 N O C O O 2 N O C O O O C NO 2
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416 and eventually drug could be cl
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422 the process of chemotherapy. De
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426 were measured. Cell incubation
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428 drug-loaded nanoparticles. It w
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430 DOX Concentration in plasma, μ
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432 Counts 10 0 150 120 90 60 30 0
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434 Tumor volume, mm 3 2500 2000 15
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436 dramatically increased intracel
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438 21.6 CONCLUSIONS In animal mode
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22 CONTENTS Polymeric Micelles Targ
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Polymeric Micelles Targeting Tumor
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23 CONTENTS cRGD-Encoded, MRI-Visib
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MRI-Visible Polymeric Micelles 467
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478 A series of recent developments
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480 O HN O O O O N O H H O H H OH O
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482 Tumor volume (mm 3 ) 2000 1500
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484 24.4 CONCLUSIONS Polymeric gene
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490 25.2 DRUG DELIVERY 25.2.1 INTRO
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494 intracellular DOX concentration
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496 H 2 N H 2 N N H O H N 2 N H NH
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498 incorporated in the PIC micelle
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502 control polymer, Exgen 500. Thi
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504 photocytotoxicity in HeLa cells
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510 H 2N H 2N H N O H N Intermediat
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512 O 2N O HN O O O O OR O HN O O O
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514 making them useful in biologica
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516 x x x x x x x x O O O O O O x O
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518 tumors with little concentratio
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27 CONTENTS PEGylated Dendritic Nan
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PEGylated Dendritic Nanoparticulate
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552 28.2.2.1 Long-Term Toxicity Stu
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558 considerably simplified using h
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562 FIGURE 28.8 PAGE electropherogr
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564 28.1.5.4 Synthesis of Tritium L
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566 10 nm Nanotechnology for Cancer
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568 Rel % 60 50 40 30 20 10 LBCB-6-
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570 25 nm (a) (b) 20.51 nm 27.82 nm
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572 architecture (fenestrated struc
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574 nanoparticle aggregates that sh
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576 harvested, weighed, and process
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578 Biodistribution of 5 nm Positiv
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580 surface Au-composite nanodevice
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582 28.2.2.2 Long-Term Toxicity of
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584 Targeted RadioTherapy (StaRT) i
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586 REFERENCES Nanotechnology for C
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596 range (!200 nm size) and can be
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30 CONTENTS Positively-Charged Lipo
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Positively-Charged Liposomes for Ta
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630 development because of poor pha
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636 FIGURE 31.1 The enhancement of
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32 CONTENTS RGD-Modified Liposomes
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RGD-Modified Liposomes for Tumor Ta
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664 of tissue specificity, and they
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666 OH N H N 2N N N Folic acid NH
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670 FIGURE 33.3 FR-mediated endocyt
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672 FR-b expression seems to be a p
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34 CONTENTS Nanoscale Drug Delivery
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Nanoscale Drug Delivery Vehicles fo
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724 The term macroemulsion is somet
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726 W Oil Water-in oil (W/O emulsio
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728 light scattering), counting (e.
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730 rhizoxin. 31,35 When lecithin w
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732 TABLE 35.3 Area Under the Perce
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734 cholesterol oleate as lipids, e
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736 REFERENCES Nanotechnology for C
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36 CONTENTS Solid Lipid Nanoparticl
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Solid Lipid Nanoparticles for Anti-
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37 CONTENTS Lipoprotein Nanoparticl
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Lipoprotein Nanoparticles as Delive
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788 i.e., the molecular targets of
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790 by apoptosis-triggering drugs.
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794 Paclitaxel / DQA (molar) 0.9 0.
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796 Considering that paclitaxel, ge
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Section 2 Polymer Conjugates q 2006
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Section 4 Polymeric Micelles q 2006
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Section 6 Liposomes q 2006 by Taylo
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