Simultaneous Measurement of Liposome Extravasation and Content Release in Tumors

Objective: The success of liposome-based drug delivery systems for tumor targeting relies on maximum extravasation of liposomes into tumor intersritium, as well as optimal release of contents from the liposomes once within the tumor. Liposome extravasation and content release are two separate proces...

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Bibliographic Details
Published in:Microcirculation (New York, N.Y. 1994) N.Y. 1994), 1997-03, Vol.4 (1), p.83-101
Main Authors: Wu, Ning Z., Braun, Rod D., Gaber, Mohamed H., Lin, Gerald M., Ong, Edgardo T., Shan, Siqing, Papahadjopoulos, Demetrios, Dewhirst, Mark W.
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacokinetics
Antibiotics, Antineoplastic - therapeutic use
Bradykinin - pharmacology
Carbocyanines
Doxorubicin - pharmacokinetics
Doxorubicin - therapeutic use
Drug Carriers
Erythrocytes - metabolism
Extravasation of Diagnostic and Therapeutic Materials
Fluoresceins - pharmacokinetics
Fluorescence
fluorescence microscopy
Fluorescent Dyes
Hematocrit
Hot Temperature
hyperthermia
liposome
Liposomes - pharmacokinetics
Mammary Neoplasms, Experimental - blood supply
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - metabolism
Microcirculation
Rats
Rhodamines
Temperature
tumor
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Summary:Objective: The success of liposome-based drug delivery systems for tumor targeting relies on maximum extravasation of liposomes into tumor intersritium, as well as optimal release of contents from the liposomes once within the tumor. Liposome extravasation and content release are two separate processes that can be individually or jointly manipulated, so a method is needed to monitor these two processes independendy and simultaneously. In this report, we describe a method to measure liposome extravasation and content release in tumor tissues growing in a rat skinfold window chamber preparation. Methods: Mixtures of liposomes containing either doxorubicin or calcein, both of which are fluorescent, and liposomes surface-labeled with rhodamine were injected intravenously. Fluorescent light intensities in a tumor region in two fluorescent channels were measured using an image-processing system. Light intensities of plasma from blood samples were also measured using this system. These measurements were used to calculate the amounts of liposomes and released contents in both plasma and tumor intersritium. The calculations were based on the fact that the liposome surface labels and contents emit fluorescent light at different wavelengths and, when encapsulated, the contents' fluorescence is self-quenched. The model included equations to account for fluorescent light "cross-contamination" by the two fluorochromes as well as equations relating the measured fluorescent light intensities to the amounts of liposomes and released contents. This method was applied to three situations in which liposome extravasation and content release were manipulated in different, predictable ways. Results and Conclusion: Our results indicate that this method can perform simultaneous, independent, and quantitative measurements of liposome extravasation and content release. This method can potentially be used to study drug delivery of other carrier systems in vivo.
ISSN:1073-9688
1549-8719
DOI:10.3109/10739689709148320