Encapsulation Of Angiotensin II in Liposomes: Characterization In Vitro and in Vivo

Abstract

The possibility of angiotensin II encapsulation in liposomes and their use as intravenous and intragastric carriers was investigated in normal rats. Up to 200 μ of angiotensin II were associated with the isolated dipalmitoyl phosphatiaylcholine/cholesterol liposomes, (approximately 50 mg lipid). After chymotrypsin digestion the latency of angiotensin II in these preparations increased to 90-98%. The angiotensin II activity and latency, as determined by a radioreceptor assay, were stable on storage at 4, 25 and 37°C for several days. Liposome-encapsulated angiotensin II of 92% latency was injected i.v. into four anesthetized rats at doses of 50-666 ng angiotensin II per kg. The blood pressure response was immediate and well above the response expected from the nonlatent angiotensin II in the injected preparations. Control animals received empty liposomes, free angiotensin II or appropriate mixtures thereof. Intragastric administration of 330 μg liposome-entrapped angiotensin II to each of two conscious rats resulted in no detectable effect on blood pressure for four hours. Liposome-encapsulated angiotensin II is considered as a model system for similar studies of other short-lived hormones or drugs. The data along with recent work with insulin (Dapergolas, G. and Gregoriadis, G. (1976) Lancett ii, 824-827) suggest that a minimum half-life of the agent to be encapsulated in liposomes is necessary for effective use of these preparations as intragastric carriers.