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  • 1
    Electronic Resource
    Electronic Resource
    Molecular sieving of red cell membranes during gradual osmotic hemolysis (1972)
    Springer
    The journal of membrane biology 10 (1972), S. 345-356 
    Details
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Rat red blood corpuscles were held stationary with respect to a continuously flowing solution in either a specially constructed centrifuge or in glass filters. The concentration of the solution was gradually decreased to cause the swelling and subsequent gradual osmotic hemolysis of the cells. The passage of the intracellular molecules —potassium, adenylate kinase, and hemoglobin—across the cell membranes and into the flowing solution was determined as a function of time. Ions and molecules begin passage across the membranes in the order of increasing molecular size. The initial flow of potassium is followed by the initial flows of hemoglobin and adenylate kinase. The flow of hemoglobin has been interpreted as the flows of hemoglobin monomers, dimers, and tetramers such that the time sequence is: potassium; hemoglobin monomer; adenylate kinase/hemoglobin dimer; and finally, hemoglobin tetramer. It is concluded that the stressed cell membrane has molecular sieving properties and that the exclusion limit (effective hole size) increases as a function of time during the initial stages of gradual osmotic hemolysis. The process of gradual osmotic hemolysis is discussed in terms of molecular sieving through stress-induced effective membrane holes. It is suggested that a portion of the membrane protein might form an elastic network which would account for the gradual increase in size and apparent homogeneity of the effective holes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01867865
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Lymphatic Transport of Liposome-Encapsulated Drugs Following Intraperitoneal Administration – Effect of Lipid Composition (1985)
    Springer
    Pharmaceutical research 2 (1985), S. 271-278 
    Details
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Tumor cells often metastasize through lymphatic channels. It follows that localization of antitumor agents in the lymphatics may be therapeutically beneficial. This study determines the extent to which lipid composition controls lymphatic transport of a model compound (14C-sucrose) in liposomes following intraperitoneal administration in rats. All liposomes tested had mean diameters of approximately 0.2 µm. Liposomes were administerd to thoracic duct cannulated rats, and 14C was quantified in thoracic lymph, several lymph nodes, blood, urine, and peritoneal wash. Changing liposome composition altered the rate of absorption of 14C from the peritoneal cavity, stability in biological fluids, and the relative ability of liposomes to be retained by lymph nodes. Stability in biological fluids (plasma and lymph) appeared to be a reasonable predictor of observed lymph node recovery. Direct measures of lymph node level alone were poor measures of the ability of liposomes to function as prototypal lymphatic drug carriers. Neutral liposomes were better at reaching the general circulation following absorption from the peritoneal cavity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016337500364
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Engineering Targeted In Vivo Drug Delivery. I. The Physiological and Physicochemical Principles Governing Opportunities and Limitations (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 333-344 
    Details
    ISSN: 1573-904X
    Keywords: drug delivery, targeted ; prodrugs ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiologically based model is presented to aid prediction of the pharmacological benefits to be derived from the administration of a drug as a targeted drug–carrier combination. An improvement in the therapeutic index and an increase in the therapeutic availability are the primary benefits sought. A measure of the former is obtained from the value of the drug targeting index, a newly derived parameter. Both the drug targeting index and the therapeutic availability are directly calculable. The minimum information needed for approximating both parameters is the candidate drug's total-body clearance and some knowledge of the target site's anatomy and blood flow. Drugs with high total-body clearance values that are known to act at target tissues having effective blood flows that are small relative to the blood flow to the normal eliminating organs will benefit most from combination with an efficient, targeted carrier. Direct elimination of the drug at the target site or at the tissue where toxicity originates dramatically improves the drug targeting index value. The fraction of drug actually released from the carrier at both target and nontarget sites can radically affect index values. In some cases a 1% change in the fraction of the dose delivered to the target can result in a 50% change in the drug targeting index value. It is argued that most drugs already developed have a low potential to benefit from combination with a drug carrier. The approach allows one to distinguish clearly those drugs that can benefit from combination with targeted in vivo drug carriers from those drugs that cannot.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016332023234
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    Paper (German National Licenses)
    Fulltext
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