Alteration in the temperature-dependent content release property of thermosensitive liposomes in plasma

Abstract

The effect of plasma components on the temperature-dependent content release property of thermosensitive liposomes has been described. Temperature-sensitive liposomes containing mitomycin C (MMC) were prepared from dipalmitoylphosphatidylcholine (DPPC liposomes) and a 7 : 3 mixture of DPPC and dipalmitoylophosphatidylglycerol (DPPC/DPPG liposomes). We defined in this study the difference in the content release between 38°C and 44°C as an index of the temperature-dependent content release efficiency (Δ% release). In the absence of rat plasma, the Δ% release of the DPPC liposomes and the DPPC/DPPG liposomes was 83% and 71%, respectively. However, when the release study was conducted with rat plasma, the Δ% release increased to about 96% for both liposomes. In addition, while the DPPC liposomes were destabilized by rat plasma below the gel-to-liquid crystalline phase transition temperature (Tm), MMC leakage from the DPPC/DPPG liposomes below Tm was suppressed by rat plasma. Moreover, the plasma protein binding onto lipid bilayer was concomitant with the gel-to-liquid crystalline phase transition and then enhanced the temperature-dependent release from the DPPC/DPPG liposomes. The possible mechanism of interaction between liposomes and plasma proteins, especially serum albumin, was discussed based on differential scanning calorimetry and protein binding experiments. © 2003 Pharmaceutical Society of Japan.