Lipid Dependent Cardio- Haemodynamic Tolerability of Liposomes in Rats

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Abstract
Rationale and Objectives: The use of contrast-carrying liposomes in diagnostic applications (1) or of haemoglobin liposomes in blood replacement therapy (2) requires infusion of large lipid doses. Saturated lipids like HSPC are often used in these formulations to render the liposomes more stable (3). Previous studies have indicated that intravenous injection of such liposome preparations can result in significant haemodynamic changes in rats (14). The purpose of this study was to systematically evaluate cardio- and haemodynamic effects of liposomes prepared from saturated and unsaturated phosphatidylcholine alone or in combination with other lipid components. Methods; Liposomes made from SPC, HSPC, DSPC, DSPC/CH, DSPC/DSPG, DSPC/CH/DSPG were infused in anaesthetized rats (total lipid dose: 300 mg lipid/kg BW) and cardio-heamodynamic parameters were measured. Results: DSPC-liposomes significantly reduced blood pressure (BP) and total peripheral resistance (TPR) by -53.7 % and -45.7 % of prevalue, respectively. Similar results were obtained for HSPC-liposomes. Marked ECG-changes were recorded for both formulations. SPC-liposomes caused a transient and moderate reduction of BP and TPR (-17.0 % and -22.3 %, respectively). Short-lasting ECG changes were also observed. The addition of cholesterol or DSPG to DSPC liposomes reduced cardiac and haemodynamic side effects in rats. Conclusion; The lipid composition of liposomes is of major importance for the incidence of cardiovascular side effects in rats. Liposomes composed of pure saturated phosphatidylcholine cause significant changes which can be diminished by the addition of other lipid components like cholesterol.