Effect of liposomal surface charge on the pharmacokinetics of an encapsulated model compound

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Abstract
The pharmacokinetics of 3H-Triamcinolone Acetonide-21-palmitate entrapped in liposomes with neutral, negative and positive surface charge was investigated in the male New Zealand White rabbit after a single intravenous bolus injection. Drug concentration–time data monitored in whole blood showed bi-exponential decay and were analysed by a least-squares regression analysis procedure to obtain pertinent pharmacokinetic parameters. The significance of the observed differences in the pharmacokinetics after administration of each type of liposome was assessed by the Analysis of Variance test method. Significant differences (p < 0·05) were found in α, β, (t0·5)α, K12, and Vc. Positive liposomes apparently encountered a larger initial apparent volume of distribution than the neutral or negative type, and consequently exhibited demonstrably lower initial blood drug concentration, (Cb)0. Liposomes with different surface properties were removed from circulation at different rates and this resulted in significant difference (p < 0·01) in the concentration of circulating liposomes an hour following injection of each type of liposome. A mean of 66 per cent of the initial concentration of positive liposomes remained in circulation an hour after injection whereas 11 and 23 per cent respectively of the neutral and negative type remained in circulation during the same time period. Liposomes with different surface properties apparently exhibited similar total body clearance of the encapsulated compound.