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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 94 (1990), S. 978-980 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: pulmonary gene medicine ; plasmid ; aerosol ; ultrasonic nebulization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study relates to the development of gene therapies for the treatment of lung diseases. It describes for the first time the use of ultrasonic nebulization for administration of plasmid/lipid complexes to the lungs to transfect lung epithelial cells. Methods. Plasmid complexed to cationic liposomes at a specific stoichiometric ratio was nebulized using an ultrasonic nebulizer. We assessed: (i) the stability of plasmid and plasmid/lipid complexes to ultrasonic nebulization, (ii) the in vitro activity of plasmid in previously nebulized plasmid/lipid complex, (iii) the in vivo transgene expression in lungs following intratracheal instillation of nebulized plasmid/lipid formulations compared to un-nebulized complexes, (iv) the emitted dose from an ultrasonic nebulizer using plasmid/lipid complexes of different size, and (v) the transgene expression in lungs following oral inhalation of aerosolized plasmid/lipid complex generated using an ultrasonic nebulizer. Results. Integrity of plasmid formulated with cationic lipids, and colloidal stability of the plasmid/lipid complex were maintained during nebulization. In contrast, plasmid alone formulated in 10% lactose was fragmented during nebulization. The efficiency of transfection of the complex before and after nebulization was comparable. Nebulization produced respirable aerosol particles. Oral exposure of rodents for 10 minutes to aerosol produced from the ultrasonic nebulizer resulted in transgene expression in lungs in vivo. Conclusions. The performance characteristics of the ultrasonic nebulizer with our optimized plasmid/lipid formulations suggests that this device can potentially be used for administering gene medicines to the airways in clinical settings for the treatment of respiratory disorders.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 6 (1989), S. 367-372 
    ISSN: 1573-904X
    Keywords: drug targeting ; site-specific delivery ; steady state ; pharmacokinetics ; pharmacodynamic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Physiological models have often been used to investigate the processes involved in drug targeting. Such a model is used to investigate some aspects of drug targeting, including the pharmacodynamics of therapeutic and toxic effects. A simple pharmacodynamic model is incorporated in a three-compartment pharmacokinetic model. Conventional administration and drug targeting are compared at steady state for the same degree of therapeutic effect. The efficiency of drug targeting is quantified as the ratio (TA) of the rates of administration of free drug or of a drug–carrier complex required to achieve this effect. Also, the ratios of drug concentrations in the toxicity compartment (DTI) or of the consequent degree of toxic effects (TI) are used to compare conventional administration with drug targeting. The kinetic characteristics of the drug–carrier complex, rate of elimination, and rate of free drug release, influence TA but not DTI or TI. The importance of these characteristics depends on the cost and toxicity of the drug–carrier complex or of the carrier alone. The pharmacodynamics of the free drug in both the target and the toxicity compartments have an important influence on TI but not on TA or DTI. As the pharmacological selectivity of the drug increases, so does TI. However, a drug with good pharmacological selectivity may not be suitable for drug targeting. TI is also very dependent on the shape of the effect–concentration curves, particularly that for toxicity. While TA increases as the rate of elimination of free drug from either central or target compartments increases, TI may actually be reduced if release of free drug is not confined to the target compartment.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 28 (1990), S. 2651-2663 
    ISSN: 0887-624X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new method is described for the preparation of sterically stabilized nanoparticles of defined size and polydispersity which are stabilized in aqueous solution by the presence of covalently linked monomethoxy-poly (oxyethylene) (MeOPOE) chains. The nanoparticles (100-270 nm mean diameter) were prepared by a process of desolvation of a graft copolymer prepared from poly(2-aminoethylmethacrylate) (PAEMA) and MeOPOE. Reproducible desolvation was achieved by the addition of sodium phosphate buffer to the copolymer in aqueous solution to give particles which were crosslinked in situ with the addition of glutaraldehyde. The size (mean diameter) and polydispersity (Q) of the particles were determined by Photon Correlation Spectroscopy (PCS). The temperature at which the desolvation reaction was performed was found to influence the particle size; at low temperatures (5-12°C), small particles were produced (99-121 nm, Q = 0.090-0.121), whereas at much higher temperatures (40-55°C), particles as large as 224-275 nm (Q = 0.138-0.127) were generated. Other parameters such as the graft copolymer concentration, the amount of glutaraldehyde added, the pH of the sodium phosphate buffer added, and the reaction time were found to be of relative insignificance in influencing the particle size. In addition to those involved in drug delivery, our method of nanoparticle preparation may be of interest to those engaged in the preparation of particulate materials and colloidal dispersions for other specific applications (e.g. stabilized photographic emulsions).
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 33 (1993), S. 453-457 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Reactions between water-insoluble and water-soluble components are often slow, giving low yields. In order to prepare glycolipids composed of polysialic acid and N-(4-(p-maleimidylphenyl)butyryl)dipalmitoyl-L-α-phosphatidylethanol amine triethylammonium salt, we used liposomes to enhance the interfacial reaction between the reagents. Thus, thiolreactive liposomes were reacted with polysialic acid cysteamine. A 70% yield was achieved with this addition reaction, and the product was isolated by dialysis and centrifugation © 1993 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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