Heat sensitive immunoliposomes

Author

Sean M. Sullivan

Date of Award

12-1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major Professor

Leaf Huang

Committee Members

Stephen J. Kennel, John Koontz, Ernesto Friere

Abstract

Heat sensitive immunoliposomes were prepared with derivatized antibody. These liposomes are able to bind specifically to target cells and to release their encapsulated contents upon brief heating. Monoclonal anti-H2K^k covalently derivatized with palmitoyl-N-hydroxysuccinimide by the method of Huang,A., Kennel,S.J. and Huang,L. J. Biol. Chem. 255, 8015 (1980). The palmitoyl antibody was injected at a controlled rate into a suspension of fused unilamellar dipalmitoylphosphati-dylcholine liposomes maintained at a constant temperature. The final protein-to-lipid ratio of the resultant liposomes with incorporated antibody (immunoliposomes) was dependent upon the injection rate of antibody and the lipid concentration. Injection of palmitoyl antibody into a liposome suspension containing 50 mM carboxyfluorescein at 41°C resulted in simultaneous antibody incorporation and entrapment of dye. The immunoliposomes were able to release entrapped dye upon heating. Furthermore, this ability was retained when the immunoliposomes were bound to the target cells. ³H-Uridine was entrapped in the heat sensitive immunoliposomes to examine the cellular uptake properties of entrapped contents upon release. The release of uridine from bound heat sensitive immunoliposomes exhibited very similar properties to those obtained for carboxyfluorescein release. The rate of uridine uptake for immunoliposome released uridine was 5 fold greater than bare liposome released uridine and 10 fold greater than that obtained for free uridine. Nucleoside uptake inhibitors were able to inhibit uptake of free uridine and uridine released from immunoliposomes showing the release to be extracellular and uridine uptake was mediated by the nucleoside transporter. These results show that a high local concentration of nucleosides released from immunoliposomes bound to their respective target cell can enhance cellular uptake thus promoting efficient drug delivery.

Recommended Citation

Sullivan, Sean M., "Heat sensitive immunoliposomes. " PhD diss., University of Tennessee, 1985.
https://trace.tennessee.edu/utk_graddiss/12644