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1st Edition

Colloidal Carriers for Controlled Drug Delivery and Targeting Modification, Characterization, and In Vivo Distribution

By Muller Copyright 1991
    ISBN 9780849377143
    379 Pages
    Published April 15, 1991 by CRC Press

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    Colloidal carriers (particles, emulsions) for intravenous administration are a promising approach to achieve controlled release and site-specific delivery of drugs. The success of the systems will depend on their ability to maintain in blood circulation (controlled release system) or to reach target cells (e.g., bone marrow, blood cells). It is well known that the surface properties of i.v. injected particles are important factors determining the organ distribution and fate in vivo. Controlled surface modification could therefore be used to direct the carriers to the desired tissues.

    This book deals with the physico-chemical characterization of colloidal drug delivery systems and the influence of these parameters upon in vitro cell uptake and in vivo tissue distribution. Within the book, several different methods and their effect on surface characterization are discussed, and the in vivo tissue distribution of nanoparticles different in size and surface properties (coatings with Poloxamer/Polaximine/ethoxylated nonylphenols) and the carrier properties are examined in detail. The book does not deal with single aspects, but offers a comprehensive treatment of the subject. As a result, the book contributes to a better understanding of the factors influencing the organ distribution of i.v. drug carriers and provides useful information for the rational design of new carriers. It succeeds in clearing the way for future developments and the optimization of carriers for controlled drug delivery.

    INTRODUCTION. THE CONCEPT OF CONTROLLED DRUG DELIVERY AND DRUG TARGETING. INTERACTION OF I.V. ADMINISTERED CARRIERS WITH BLOOD COMPONENTS AND THE RETICULOENDOTHELIAL SYSTEM. IN VIVO FATE OF I.V. ADMINISTERED DRUG CARRIERS. BIODEGRADABLE CARRIERS FOR DRUG DELIVERY. LOCALIZATION OF CARRIERS IN THE TARGET TISSUE. TARGETING WITH I.V. ADMINISTERED CARRIERS-POTENTIALS AND LIMITATIONS. MODIFICATION OF DRUG CARRIERS. SURFACE MODIFICATION BY POLYMER ADSORPTION. COATING WITH POLOXAMER AND POLOXAMINE POLYMERS. COATING WITH POLYOXYLATED ALKYL PHENOLS. COATING WITH PHOSPHOLIPIDS. COATING WITH MISCELLANEOUS ETHOXYLATED COMPOUNDS. GAMMA-IRRADIATION AND PLASMA ETCHING. Effects of Irradiation and Plasma Etching on Polymers. Materials and Methods. Treatment of Polyhydroxybutyrate (PHB). Summary. CHARACTERIZATION OF CARRIERS. MODEL CARRIERS. SIZE DETERMINATIONS. Importance of Size for Drug Carriers. Methods and Experimental. Results of Size Determinations. CHARGE DETERMINATIONS. Influence of Carrier Charge on In Vivo Fate. Laser Doppler Anemometry (LDA). Amplitude Weighted Phase Structuration (AWPS). SURFACE HYDROPHOBICITY. Importance of Surface Properties for Drug Carriers. Rose Bengal Binding Methods. Hydrophobic Interaction Chromatography (HIC). Aqueous Two Phase Partitioning. CHEMICAL ANALYSIS OF THE CARRIER SURFACE. Static Secondary Ion Mass Spectrometry (SSIMS). SSIMS Analysis of Carriers. DETERMINATION OF CFT OF COATED CARRIERS. Theoretical and Experimental. Results of CFT Determination. Summary. NON-BIODEGRADABLE MODEL CARRIERS. PROBLEMS ASSOCIATED WITH THE USE OF MODEL CARRIERS. PRODUCTION OF POLYSTYRENE MODEL PARTICLES. Materials. Material Purification. Particle Production. INFLUENCE OF PRODUCTION PARAMETERS ON LATEX SIZE. INCORPORATION OF COLLOIDAL GOLD IN LATEX MODEL CARRIERS. PRODUCTION OF LATEX PARTICLES OF A MEAN SIZE BELOW 100 nm. SUMMARY. BIODEGRADABLE POLYMERIC CARRIERS. BIODEGRADABLE POLYMERS FOR DRUG CARRIERS. MATERIALS AND METHODS. PRODUCTION OF CARRIERS. Emulsification Evaporation Technique. Particle Production By Microfluidization. Purification and Isolation of Particles. RADIOLABELLING OF PARTICLES. Labelling with Iodine-131. Labelling with Indium-111. DRUG INCORPORATION AND RELEASE PROFILES. BIODEGRADABLE FAT EMULSION CARRIERS. PARENTERAL FAT EMULSIONS AS DRUG CARRIERS. MATERIALS AND METHODS. PRODUCTION OF EMULSION CARRIERS. CHARACTERIZATION OF POLOXAMER 188 EMULSION CARRIERS. STABILITY TESTING OF EMULSION CARRIERS. Freeze-Thaw Cycling. Constant Freeze Test. Stability Following Electrolyte Addition. SUMMARY. CELL CULTURES AS IN VITRO TEST SYSTEM FOR DRUG CARRIERS. APPLICATIONS OF CELL CULTURE TEST SYSTEMS. PHAGOCYTOSIS STUDIES WITH PERITONEAL MOUSE MACROPHAGES. Method. Phagocytosis of Poloxamer and Poloxamine Coated Latex Particles. TOXICITY STUDIES IN HEPATOCYTE CULTURES. Method. Interaction of Ethoxylated Surfactants with Hepatocytes. IN VIVO DISTRIBUTION OF CARRIERS. GAMMA-SCINTIGRAPHY FOR THE DETERMINATION OF ORGAN DISTRIBUTION AND FATE IN THE BODY. EXPERIMENTAL. ORGAN DISTRIBUTION OF POLOXAMER/POLOXAMINE COATED CARRIERS. Organ Distribution of 142 nm Model Carriers. Organ Distribution of 383 nm Model Carriers. Organ Distribution of 496 nm Model Carriers. Organ Distribution of 910 nm Model Carriers. The Organ Distribution of Different Sized Model Carriers. ORGAN DISTRIBUTION OF ETHOXYLATED NONYLPHENOL COATED LATEX. Organ Distribution of Gafac RE960 Coated 76 nm Latex. Organ Distribution of Antarox C0990 Coated 142 nm Latex. Organ Distribution of Antarox C0990 Coated 76 nm Latex. Organ Affinity of Ethoxylated Nonylphenol Coated Latex. ORGAN DISTRIBUTION OF CARRIERS AND FAT EMULSIONS SURFACE-MODIFIED WITH ETHOXYLATED MONOGLYCERIDES. BODY DISTRIBUTION OF BIODEGRADABLE PHB CARRIERS. Distribution of the Free Label. Organ Distribution of Uncoated PHB Nanoparticles. Distribution of Poloxamine 908 Coated PHB Nanoparticles. Distribution of PHB Nanoparticles Surface-Modified with Polyvinyl Alcohol (PVA). SUMMARY. RELATION OF THE IN VIVO DISTRIBUTION TO THE SURFACE CHARACTERISTICS OF THE CARRIERS. SURFACE HYDROPHOBICITY OF POLOXAMINE 908 AND POLOXAMER 407 COATED POLYSTYRENE MODEL CARRIERS. Characterization of Coated 60 nm Latex Particles. Characterization of Coated 142 nm Latex Particles. Characterization of Coated 383 nm Latex Particles. Characterization of Coated 496 nm Latex Particles. Characterization of Coated 910 nm Latex Particles. Characterization of Coated 5600 nm Latex Particles. Summary of the Surface Hydrophobicities of Poloxamine 908 and Poloxamer 407 Coatings on Particles Different in Size. SURFACE HYDROPHOBICITY OF ANTAROX C0990 COATED 67 nm CARRIERS. SURFACE HYDROPHOBICITY OF EMULSIONS CARRIERS. Surface Hydrophobicity of Egg Lecithin Emulsions. Surface Hydrophobicity of Poloxamine and Poloxamer Emulsion Carriers. Comparison of Emulsion and Coated Polymeric Carriers. SURFACE HYDROPHOBICITY OF PHB CARRIERS. HIC Investigations of PHB Carriers. Comparison of Surface Hydrophobicity of PHB Carriers and Coated Latex Model Carriers. THICKNESS OF COATING LAYERS ON LATEX PARTICLES DIFFERENT IN SIZE. CHARGE MEASUREMENTS OF DRUG CARRIERS. Charge Measurements on Coated Polystyrene Latex. Charge Measurements on Fat Emulsions. Charge Measurements on PHB Carriers. SUMMARY OF SURFACE CHARACTERIZATION. SUMMARY: RATIONAL DESIGN OF I.V. DRUG CARRIERS-THEORY OF FACTORS DETERMINING THEIR IN VIVO DISTRIBUTION. REFERENCES. APPENDICES. CHEMICALS. MANUFACTURERS ADDRESSES. ACKNOWLEDGEMENTS. SUBJECT INDEX. c. 375 pp., 227 figures, 84 tables, due January 1991, ISBN 0-8493-7714-5.

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