Active Targeting Strategies in Cancer with a Focus on Potential Nanotechnology
3.2 Nanoparticle 3.2.1 Composition and Biocompatibility 22 23 3.3 Nanoparticle 3.3.1 Inherent 3.3.2 Complicating 3.3.3 Safety 3.4 Targeting to Cancer 3.4.1 Cell Surface 3.5 Targeting to 3.5.1 Aberrant 3.5.2 Metabolic 3.6 Fate of 3.6.1 Site of Initial 3.6.2 Distribution to Specific 3.6.3 Intracellular Uptake and
Surface Characteristics
Surface characteristics contribute to the nanoparticle's solubility, aggregation tendency, ability to traverse biological barriers such as a cell wall , biocompatibility, and targeting ability. The nanoparticle surface is also responsible for interaction and binding with plasma proteins in vivo, which in turn may alter the nanoparticle's distribution and pharmacokinetics. For multifunctional nanoparticles, modifying agents are often attached to the surface to bind to receptors in target tissues...
Aptamerdrug Conjugates For Targeted Cancer Therapy
The clinical utility of radioimmunoconjugates and chemoimmunoconjugates in cancer treatment is well documented with several examples of each in clinical practice or under development at this time.123-125 More recently aptamer conjugates for cancer therapeutic and diagnostic appli-cations,14,23,108,116,118-120,126 biosensors,127-129 flow cytometry,130 ELISAs,131,132 and capillary electrophoresis for separation technology have been discribed.40,133 As noted in Section 16.2, aptamers have distinct...
Chemistry
PG is usually prepared by removing the benzyl protecting group of poly g-benzyl-l-glutamate that is attained by polymerization of g-benzyl-l-glutamate N-carboxyanhydride NCA monomer.4 Direct phosgenation of g-benzyl-l-glutamate produces the corresponding NCA monomer.5,6 In this reaction, g-benzyl-l-glutamate is suspended in a dry inert solvent such as ethyl acetate, dioxane, or tetrahydrofuran, and it is allowed to heterogeneously react with the cyclizing reagent that is normally triphosgene....
Apoptosis and Mitochondrial Dysfunction
Nanoparticle-induced cell death can occur by either necrosis or apoptosis, processes that can be distinguished both morphologically and biochemically. Morphologically, apoptosis is characterized by perinuclear partitioning of condensed chromatin and budding of the cell membrane to form apoptotic bodies, whereas necrosis is characterized by cellular swelling oncosis and bleb-bing of the cell membrane.109 In vitro studies have demonstrated the ability of nanoparticles, such as dendrimers and...
Sp1049c
SP1049C is a doxorubicin-loaded Pluronic copolymer micelle formulation developed by Kaba-nov's group and Supratek Inc. Montreal, Canada . In this formulation, doxorubicin is physically encapsulated in micelles assembled from two different types of Pluronic copolymers, L61 and F127 in a 1 8 w w ratio.26 In October 2005, SP1049C was granted orphan drug status by the FDA for the treatment of oesophageal carcinoma based on results from the phase I study meanwhile, its phase II clinical trial...
Preparation of Block Copolymer Micelle Formulations
The selection of the appropriate preparative technique for micelle formation is largely based on the solubility of the copolymer and the drug in aqueous media. There are several methods that have been developed for the preparation of drug-loaded block copolymer micelles, including the direct dissolution method, evaporation method, and dialysis method as depicted in Figure 17.1. The direct dissolution method is employed for block copolymers that are relatively soluble in water e.g., Pluronic ....
Nk911
NK911 is a doxorubicin-loaded PEG-b-PAsp copolymer micelle formulation developed by Kataoka and co-workers. Doxorubicin is both physically entrapped in the micelle core and chemically conjugated to the aspartic acid side chains of the core-forming block via amide linkages. NK911 is currently undergoing phase II clinical trial evaluation for efficacy and toxicity profiles. The formulation entered phase I in 2001, and the results from this trial revealed that NK911 exhibits a longer circulation...
Research At The Fda On Nanotechnology
Although the FDA is a regulatory agency, it is also engaged in a number of research activities. However, the FDA recognizes that science supported by research provides the foundation for sound regulation. As such, the FDA is interested in research projects that can address specific regulatory needs. As an example, FDA has a grants program in support of orphan products research and development. The FDA does not have a grants program to support other research in non-FDA laboratories....
List Of Abbreviations
,N -pentaacetic acid Cyclohexyl-diethylenetriamine pentaacetic acid acid Tissue inhibitors of matrix metalloproteinases
Examples of Aptamers for Targeted Delivery
Since their original description in 1990, aptamers have been isolated to a wide variety of targets, including intracellular proteins, transmembrane proteins, soluble proteins, carbohydrates, and small molecule drugs. As of the submission of this chapter, 624 articles related to aptamers have been published, and more than 200 aptamers have been isolated comprehensively listed in the Aptamer Database ,51 and one aptamer, macugen pegaptanib sodium , against the VEGF165 protein was recently...
Nanotechnology for Cancer Therapy
Taylor amp Francis Group Boca Raton London New York Taylor amp Francis Group, an informa business 6000 Broken Sound Parkway NW, Suite 300 2007 by Taylor amp Francis Group, LLC CRC Press is an imprint of Taylor amp Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper International Standard Book Number-10 0-8493-7194-5 Hardcover International Standard Book Number-13 978-0-8493-7194-3 Hardcover This book contains...