In Vivo Distribution of Poly Alkyl Cyanoacrylate Nanoparticles

Colloidal drug carriers such as liposomes and nanoparticles are able to modify the distribution of an associated substance. They can therefore be used to improve the therapeutic index of drugs by increasing their efficacy or reducing their toxicity. The polymer nanoparticles, particularly PACA nanoparticles, have attracted considerable attention as potential drug delivery systems, not only for their enhancement of therapeutic efficacy but also because they reduce the toxicity associated with a...

Nanoparticle Characteristics

Although nanoparticles can be prepared from a wide variety of materials (inorganic salts, lipids, synthetic organic polymers, polymeric forms of amino acids, nucleic acids, etc.), this chapter will primarily focus on those prepared from materials that would be considered sufficiently safe for repeated systemic administrations and or would be perceived to have an acceptable safety profile that would warrant use in man. In general, it is desirable for nanoparticles...

Chemoembolization Using Alkylcyanoacrylates

HCC is the most common liver tumor, with heterogeneity in the tumor behavior and the underlying liver disease. Recent combinations such as cisplatin, interferon, Adriamycin, and 5-FU are extremely toxic and yield response rates of only 20 , with no survival advantage compared to supportive care alone.184 Higher concentrations of cancer chemotherapeutic agents can be delivered directly to the HCC via the hepatic arterial route. Considering that this route is the major vascular supply of these...

Blood Contact Properties

One important aspect of nanoparticle used for medical applications is the assurance that they will not cause toxicity to blood elements when injected into a patient. Hemolysis (i.e., damage to red blood cells) can lead to life-threatening conditions such as anemia, hypertension, arrhythmia, and renal failure. In our laboratory we have developed a protocol to evaluate hemolytic properties of nanoparticles based on the existing ASTM International standard used to characterize other...

Passive Targeting And The Epr Effect

Although active targeting may be achieved through targeting to folate receptors, angiogenesis, or targets more specific to the cancer being treated, some enhancement of treatment to cancers on account of the EPR effect cannot be ignored and should be utilized until more specific targeting systems can be developed. Preparation of nanoparticle systems that can avoid uptake by the reticuloendothelial system (RES) is essential, and such particles are often referred to as stealth nanoparticles. The...

Most Common PEOModified PLAA Micelles Investigated for Drug Delivery

Development Development Development Development Clinical trials phase I Electrostatic complexationc P(Asp) Cisplatin a Most common chemical structures shown in Figure 18.5. b Most common chemical structures shown in Figure 18.6. c Most common chemical structures shown in Figure 18.7. Development Development Development Development Clinical trials phase I For the synthesis of PEO-b-PLAA block copolymers, a-methoxy-u-amino PEO has been used as the initiator. Synthesis of...

Active Targeting Strategies in Cancer with a Focus on Potential Nanotechnology Applications

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

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...

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...

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...

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...