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 μg/ml ADR to yield the MDR lines UV-2237M/ADRR (ADR-1) and UV-2237M/ADR^RR (ADR-10), respectively. VLB encapsulated in MLV composed of phosphatidylcholine (PC) and phosphatldylserine (PS) (7:3 molar ratio) was hydrophobic, occupied an internal space equivalent of 6.13 (μl/μmol, and was stable in medium at 37°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.