Overcoming murine tumor cell resistance to vinblastine by presentation of the drug in multilamellar liposomes consisting of phosphatidylcholine and phosphatidylserine.
We determined whether vinblastine (VLB) encapsulated within multilamellar vesicle-liposomes (MLV) would reverse target cell resistance to the drug exhibited by the UV-2237M murine fibrosarcoma and its Adriamycin (ADR)-selected multidrug resistant (MDR) variants. Resistant fibrosarcoma cells were grown in medium containing 1 and 10 micrograms/ml ADR to yield the MDR lines UV-2237M/ADRR (ADR-1) and UV-2237M/ADRRR (ADR-10), respectively. VLB encapsulated in MLV composed of phosphatidylcholine (PC) and phosphatidylserine (PS) (7:3 molar ratio) was hydrophobic, occupied an internal space equivalent of 6.13 microliters/mumol, and was stable in medium at 37 degrees C for up to 6 days. The 50% inhibitory concentrations (IC50) of VLB were 2, 25, and 70 ng/ml for the parent, ADR-1, and ADR-10 cell lines, respectively. VLB in MLV significantly enhanced sensitivity of tumor cells to VLB. The respective IC50 of liposomal VLB were 0.5, 5.7, and 12 ng/ml for the parent, ADR-1, and ADR-10 lines. MLV containing saline were not toxic to the cells. These data indicate that presentation of VLB entrapped in PC:PS MLV provides a method to overcome tumor cell resistance to this drug.
Seid
C A
CA
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Fidler
I J
IJ
Clyne
R K
RK
Earnest
L E
LE
Fan
D
D
D000818:Animals; D004337:Drug Carriers; D004351:Drug Resistance; D008081:Liposomes / Q000032:analysis; D051379:Mice; D010713:Phosphatidylcholines / Q000032:analysis*; D010718:Phosphatidylserines / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000008:administration & dosage* / Q000494:pharmacology
D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D014747:Vinblastine