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  • 1
    Electronic Resource
    Electronic Resource
    Generation of pH-sensitive liposomes: use of large unilamellar vesicles containing N-succinyldioleoylphosphatidylethanolamine (1985)
    s.l. : American Chemical Society
    Biochemistry 24 (1985), S. 5967-5971 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00342a042
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Identification of vesicle properties that enhance the antitumour activity of liposomal vincristine against murine L1210 leukemia (1993)
    Springer
    Cancer chemotherapy and pharmacology 33 (1993), S. 17-24 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of vesicle lipid composition, size and drug-to-lipid ratio on the antitumour activity of liposomal vincristine was assessed in the murine L1210 ascitic leukemia model. A pH gradient-dependent entrapment procedure was used to encapsulate vincristine and allowed such vesicle properties to be independently varied. Free vincristine delivered i.v. at the maximum tolerated dose (2.0 mg/kg) resulted in a 27.8% increase in the life span (ILS) of mice inoculated i.p. with L1210 cells. Encapsulation of the drug in egg phosphatidylcholine/cholesterol vesicles did not significantly increase the antitumour efficacy of vincristine (ILS, 38.9%). In contrast, administration of vincristine entrapped in vesicles composed of distearoylphosphatidylcholine (DSPC)/cholesterol resulted in ILS values as high as 133%. This enhanced antitumour activity of the DSPC/cholesterol formulations was sensitive to the size of the liposomes; increasing the vesicle size from 100 nm to 1 μm decreased the ILS from 133.3% to 55.6% at a drug dose of 2.0 mg/kg. Decreasing the drug-to-lipid ratio from 0.1∶1 to 0.05∶1 (w/w) had negligible effects on the activity of liposomal vincristine; however, a further decrease in the drug-to-lipid ratio to 0.01∶1 (w/w) decreased the antitumour potency at all drug doses studied. Pharmacology studies indicated that the antitumour activities of free and various liposomal forms of vincristine correlated well with the residence time of the drug in the circulation. These studies indicate that efforts to enhance the therapeutic activity of vincristine through liposome encapsulation must address not only the circulation life-time of the vesicle systems but also the capacity of the liposomes to retain entrapped drug in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686017
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  • 3
    Electronic Resource
    Electronic Resource
    Studies on the myelosuppressive activity of doxorubicin entrapped in liposomes (1990)
    Springer
    Cancer chemotherapy and pharmacology 27 (1990), S. 13-19 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The myelosuppressive activity of doxorubicin encapsulated in liposomes of differing lipid composition and size was quantified in mice by measurement of changes in spleen weight, peripheral white blood cells (WBC), and bone marrow nucleated cells. Following i. v. administration of free doxorubicin at a dose of 20 mg/kg, a 90% reduction in marrow cellularity was observed on day 3. The marrow nucleated cell count was similar to control values by day 7. Administration of an equivalent dose of doxorubicin that was encapsulated in large (diameter, ∼1.0 μm) egg phosphatidylcholine/cholesterol (EPC/Chol)(molar ratio, 55∶45) liposomes induced an 80% reduction in bone marrow cellularity that lasted for periods of 〉7 days. Similar results were obtained following administration of large (1.0 μm) liposomal doxorubicin systems formulated with distearoylphosphatidylcholine/cholesterol (DSPC/Chol) (molar ratio 55∶45). In contrast, liposomal doxorubicin prepared using small (diameter, ∼0.1 μm) DSPC/Chol liposomes induced only a 40% reduction (day 3) in bone marrow cellularity, which returned to control values by day 7. Other indicators of doxorubicin-mediated myelosuppressive activity (spleen weight loss and peripheral leukopenia) correlated well with changes observed in marrow cellularity. An exception to this, however, was observed in animals treated with small (0.1-μm) DSPC/Chol liposomal doxorubicin, which displayed peripheral leukopenia for periods of 〉14 days. This extended leukopenia was not observed following administration of small (0.1-μm) EPC/Chol liposomal doxorubicin. Marrow-associated liposomal lipid and doxorubicin were quantified to determine if the extent of doxorubicin-mediated myeloid toxicity could be correlated to changes in biodistribution of the entrapped drug. It was demonstrated that 10–20 times more doxorubicin is delivered to the bone marrow when the drug is given encapsulated in largeliposomes than when it is associated with small liposomes. These data are useful in defining characteristics of liposomal preparations that modulate the myelosupressive behaviour of entrapped antineoplastic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689270
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  • 4
    Electronic Resource
    Electronic Resource
    Transfer of liposomal drug carriers from the blood to the peritoneal cavity of normal and ascitic tumor-bearing mice (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 137-146 
    Details
    ISSN: 1432-0843
    Keywords: Liposomes ; doxorubucin ; extravasation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previously we have demonstrated that the L1210 antitumor activity of liposomal doxorubicin increased significantly as the size of the liposomal carrier was reduced from 1.0 to 0.1 μm. It is demonstrated herein that empty and drug-loaded small (0.1-μm diameter) liposomes accumulate efficiently into the peritoneal cavity of normal and ascitic L1210 tumor-bearing animals following i.v. administration. In normal mice injected with 100 nm DSPC/chol liposomal doxorubicin (drug-to-lipid ratio of 0.2; wt/wt) approximately 2.8 μg drug could be recovered from the peritoneal cavity following peritoneal lavage at 24 h. Although this represents only 0.7% of the injected doxorubicin dose, this level of drug is 2 orders of magnitude greater than that achieved following administration of an equivalent dose of free drug (20 mg/kg). The drug levels achieved within the peritoneal cavity are dependent on the physical characteristics (size, drug-to-lipid ratio and lipid composition) of the liposomes employed. Optimal delivery is obtained employing 100 nm DSPC/chol liposomal doxorubicin, a vesicle system that is known to retain entrapped drug following i.v. administration and exhibits extended circulation lifetimes. Analysis of drug and liposome distribution within the peritoneal cavity of normal mice indicates that as much as 50% of the measured doxorubicin and liposomal lipid is cell-associated. Flow cytometric analysis of the peritoneal cells demonstrated that cell-associated doxorubicin resides almost exclusively within resident peritoneal macrophages. The increased delivery of doxorubicin to the peritoneal cavity of normal mice following i.v. administration of small (0.1-μm) liposomal doxorubicin is correlated with a pronounced (〉90%) and prolonged (〉14-day) suppression of resident peritoneal cells. Liposomal drug accumulation increased dramatically in animals with an established L1210 ascitic tumor. More than 5% of the injected dose was found in the peritoneal cavity of these animals 24 h after treatment with DSPC/chol liposomal doxorubicin as compared with a value of 0.03% of the injected dose achieved with free drug. It is proposed that accumulation of liposomes into the peritoneal cavity of normal and tumor-bearing mice may serve as a useful model for characterizing factors mediating the transfer of liposomes from the vascular compartment to extravascular sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685931
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  • 5
    Electronic Resource
    Electronic Resource
    A microassay for the rapid and selective binding of cells from solid tumors to mouse macrophages (1986)
    Springer
    Cancer immunology immunotherapy 22 (1986), S. 125-131 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A microassay was developed to study the rapid binding characteristics of murine macrophages activated by gamma interferon and muramyl dipeptide to adherent neoplastic or nonneoplastic target cells. The binding of tumor cells to both activated and nonactivated macrophages was time- and temperature-dependent, and independent of tumor cell type. Activated macrophages bound more tumor cells than nonactivated macrophages. The initial binding of macrophages to target cells did not necessarily lead to lysis. First, primed macrophages bound tumor cells but did not lyse them, and second, nonactivated macrophages bound nontumorigenic cells without subsequent lysis. The rapid binding assay described here could prove useful in investigating the recognition mechanism(s) between macrophages and tumor cells derived from solid primary and metastatic cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199126
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    In vitro activation of tumoricidal properties in mouse macrophages using the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) incorporated in liposomes (1988)
    Springer
    Cancer immunology immunotherapy 27 (1988), S. 1-6 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the ability of free or liposome-incorporated synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) to generate tumoricidal properties in mouse macrophages. As FMLP contains three hydrophobic amino acid residues, it can readily be incorporated into multilamellar vesicles (MLV) consisting of phosphatidylcholine (PC) and phosphatidylserine (PS). The incorporation of FMLP into MLV with a PC:PS ratio of 7:3 mol at FMLP concentrations of up to 10−4 M did not affect the phagocytosis of liposomes by mouse peritoneal macrophages. Studies with radioactive FMLP revealed that higher levels of FMLP can be delivered to macrophages by liposomes than in the free, nonencapsulated form. Treatment of mouse macrophages with liposome-encapsulated FMLP, but not with free FMLP, generated tumoricidal properties in the macrophages. The mechanism appears to involve an intracellular site since 100-fold concentrations of free FMLP or free N-acetyl-methionyl-leucyl-phenylalanine, the FMLP agonist, failed to competitively inhibit the macrophage's tumoricidal properties generated by liposome-encapsulated FMLP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205750
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  • 7
    Electronic Resource
    Electronic Resource
    The systemic activation of macrophages by liposomes containing immunomodulators (1985)
    Springer
    Springer seminars in immunopathology 8 (1985), S. 413-428 
    Details
    ISSN: 1432-2196
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions The demonstration that appropriately activated macrophages can destroy microorganisms and cancer cells has prompted an intense search to identify agents which can render these cells active in vivo. Several natural products, e. g., lymphokines or synthetic molecules, e. g., MDP can produce the tumoricidal state in macrophages. The in vivo use of these agents has been limited, since they have a very short half life. Liposomes offer a most useful carrier system to transport agents to phagocytic cells in vivo. Once in the circulation, liposomes are cleared by phagocytic cells and this passive localization provides an effective mechanism for targeting liposome-entrapped materials to macrophages. In this review we have described the exploitation of this mechanism to deliver lymphokines or other synthetic molecules to macrophages in situ. Since not all liposomes home equally to macrophages, there is still a great need to identify vesicles with ideal properties for this task. The potential application of liposome encapsulated agents to activate macrophages is tremendous. Only future studies will determine the effectiveness and limitations for activated macrophages in enhancing host defense against infections and cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01857394
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