Stability of lipid vesicles in tissues of the mouse: a gamma-ray perturbed angular correlation study

The rate of phospholipid vesicle disruption in specific tissues of the mouse was followed by gamma-ray perturbed angular correlation (PAC) spectroscopy. In these studies, high levels of 111In-nitrilotriacetic acid complex are contained in unilamellar vesicles consisting of distearoyl phosphatidylcholine, cholesterol, and small amounts of other lipids which modify the surface properties. The PAC technique monitors the extent of vesicle breakup by measuring a time-integrated perturbation factor, less than G22 (infinity) greater than. As the vesicles are broken open in vivo, the released 111In3+ ions quickly bind to macromolecules and the less than G22 (infinity) greater than value decreases substantially. After administration of vesicles by various routes (intravenous, intraperitoneal, subcutaneous, and oral), the radioactivity and less than G22 (infinity) greater than values were determined for several tissues at intervals up to 24 hr. We conclude from these data that (i) the PAC technique in conjunction with standard gamma counting methods provides unique information on the condition and location of vesicles in specific tissues, (ii) significant differences in vesicle integrity are found in various tissues, and (iii) both the means of administration and the presence of surface charge affect the vesicle stability and distribution. The carbohydrate analogues of cholesterol affect vesicle stability but not distribution.