In-vitro cytotoxic/cytostatic activity of anionic liposomes containing vinblastine against leukaemic human cell lines

Liposomes prepared from lipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with cholesterol were used to investigate the percentage of vinblastine encapsulation and the influence of lipid composition on the retention properties of vinblastine in buffer as well as in cell culture medium. Differential scanning calorimetry (DSC) was applied, to study the effect of cholesterol on the phase transition temperature and on the ΔH of the two liposome formulations. The cytotoxic and cytostatic activity of the liposome‐encapsulated vinblastine was also examined against six leukaemic human cell lines. The results showed that encapsulation of vinblastine into liposomes was greater than 98% with a drug‐phospholipid molar ratio of 0.13‐0.18. The major improvement in vinblastine retention in buffer as well as in culture medium was achieved by employing DPPG. The DSC data showed that vinblastine exerted a more perturbing effect in DPPC‐cholesterol bilayers than in DPPG‐cholesterol bilayers and this may explain their lower retention time. The 50% growth‐inhibiting (GI50) and cytostatic (TGI) activity of liposomal vinblastine did not seem to be affected by the type of the liposome while the 50 % cytotoxic activity (LC50) was affected in four out of the six cell lines tested. The parameters GI50, TGI and LC50 were estimated according to the instructions given by the NCI.