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  • 1995-1999  (3)
  • molecular weight between crosslinks (Mc)  (2)
  • Key words Immunoliposome  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Characterization of organ-specific immunoliposomes for delivery of 3′,5′-O-dipalmitoyl-5-fluoro-2′-deoxyuridine in a mouse lung-metastasis model (1995)
    Springer
    Cancer chemotherapy and pharmacology 35 (1995), S. 447-456 
    Details
    ISSN: 1432-0843
    Keywords: Key words Immunoliposome ; Lipophilic prodrug ; Lung targeting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A previous study has shown that lipophilic prodrugs can be delivered efficiently to normal lung endothelium by incorporation into liposomes covalently conjugated to monoclonal antibody (mAb) 34A against the lung endothelial anticoagulant protein thrombomodulin. In the present study, the potential use of these lung-targeted immunoliposomes (34A-liposomes) for delivery of a lipophilic prodrug, 3′,5′-O-dipalmitoyl-5-fluoro-2′-deoxyuridine (dpFUdR), to the tumor-bearing lung was examined using BALB/c mice bearing experimental lung metastasis induced by i.v. injection of EMT-6 mouse mammary tumor cells. Immunohistochemical examination of the tumor-bearing lung showed specificity of mAb 34A to lung endothelium. Tumor cells appeared to localize just outside of the normal blood vessels and were within a small diffusion distance from the mAb 34A-binding sites. 111In-labeled 34A-liposomes containing monosialoganglioside (GM1) were prepared that included [3H]-dpFUdR at 3.0 mol% in the lipid mixture. In vitro cell binding studies further demonstrated that 34A-liposomes bound specifically to normal mouse lung cells that expressed thrombomodulin but not to EMT-6 cells. Biodistribution study showed efficient and immunospecific accumulation of [3H]-dpFUdR incorporated into 34A-liposomes in the lung at a level parallel with that of 111In-labeled 34A-liposomes, indicating that the drug is delivered to the target organ in intact liposomes. Liposomal dpFUdR appeared to be metabolized in the lung to the parent drug FUdR at a rate slower than in the liver and spleen. Furthermore, treatment of lung-metastasis-bearing mice with dpFUdR incorporated into 34A-liposomes on days 1 and 3 after tumor cell injection resulted in a significant increase in the median survival time of treated mice as compared with control mice (%T/C value, 165%). dpFUdR either dispersed in emulsion or incorporated into antibody-free liposomes was ineffective in prolonging the survival of mice. These results indicate the potential effectiveness of organ-specific immunoliposomes containing a lipophilic prodrug for the targeted therapy of metastatic tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686828
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of a Statistical Model for the Formation of Poly [Acryloyl Hydroxyethyl Starch] Microspheres (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 475-482 
    Details
    ISSN: 1573-904X
    Keywords: Flory-Rehner model ; dynamic and equilibrium swelling ; molecular weight between crosslinks (Mc) ; degree of derivatization(DD) ; molar ratio (MR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the network structure of Poly (Acryloyl Hydroxyethyl Starch) (Ac-HES) microspheres and test the theoretical model and the hypothesis that the rate of swelling of microspheres is inversely related to the extent of crosslinking. Methods. Microspheres were prepared with varying degrees of derivatization (DD) and molar ratios (MR) and subjected to the characterization of matrix structure by dynamic and equilibrium swelling studies utilizing direct microscopic observation and the Flory-Rehner equation. The dependence of average molecular weight between crosslinking Mc, on DD and MR were compared to test the validity of the model. Results. Study of the dependence of Mc on the microspheres preparation parameters, DD and MR, showed that at constant MR, the Mc decreased with DD, while at constant DD, the Mc initially decreased with MR to a minimum, and then increased with MR, complying with the model prediction. Dynamic swelling of microspheres showed a monotonical increase to equilibrium size featured by two time variables, Tp and Teq, that were dependent on Mc; this permitted a conceptual view of the general structure of the Ac-HES microspheres. The Mc, which was more accurately determined by the weight method (as opposed to volume method), was independent of the size of microspheres although there was evidence of variation among particles within a batch. Conclusions. The results validated the model in describing the polymerization/crosslinking reaction of the Ac-HES microsphere system and suggested that Mc is the principal factor in controlling release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012199500072
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Development of a Statistical Model for the Formation of Poly [Acryloyl Hydroxyethyl Starch] Microspheres (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 469-474 
    Details
    ISSN: 1573-904X
    Keywords: poly(Acryloyl Hydroxyethyl Starch) microspheres ; molecular weight between crosslinks (Mc) ; degree of derivatization (DD) ; molar ratio (MR) ; link probability generating function (LPGF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a mathematical model for predicting the molecular weight between crosslinks, Mc, of poly[Acryloyl Hydroxyethyl Starch] (Ac-HES) microspheres system and to identify and evaluate the key microsphere preparation parameters which affect the Mc of the formed microsphere structure based on the developed model. Methods. Link probability generating functions (LPGFs) based on the classical branching theory were used to derive a model for the calculation of Mc for the Ac-HES system. Based on the developed model, simulation was made to study the effects of the microsphere preparation variables on Mc of the formed microspheres. The process variables were the degree of derivatization (DD) of the Ac-HES, the molar ratio (MR) of the Ac-HES to acrylamide monomer, the fractional conversion of the unsaturation (α), the initiator efficiency (f), the molar concentration of initiator (I), the fraction of intramolecular cyclization (c), and the total weight of the reactable monomer and polymer (s). Results. A model to describe the crosslinking reaction of Ac-HES system and predict Mc was developed. Simulation based on the model showed that Mc decreased as α increased and reached a limiting value before total conversion. At constant α, Mc initially decreased with MR to a minimum and then increased with MR; while Mc decreased monotonically with DD. I and c affected Mc only at very low α and changes in s and f had no effect on Mc. Conclusions. Simulation based on the model suggested that the most important microsphere preparation parameters influencing Mc of the Ac-HES system are the number of functional groups on the Ac-HES (DD) and the stoichiometry (MR) of the crosslinking reaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012111116002
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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