Fate of Lipid Vesicles in vivo: A Gamma-Ray Perturbed Angular Correlation Study

Abstract

The structural integrity of unilamellar vesicles has been studied in vitro and in vivo by use of gamma-ray perturbed angular correlation techniques. These studies utilize 111In3+ weakly bound to the chelator nitrilotriacetic acid as a probe to monitor the percentage of intact vesicles. When complexes of 111In3+ and nitrilotriacetic acid is encapsulated in vesicles, 111In3+ exhibits a fast tumbling rate. Upon alteration of the membrane, 111In3+ is released from the liposomes and becomes bound to macromolecules, consequently exhibiting a decrease in 111In3+ tumbling rate. The in vitro experiments show that the present technique is capable of determining quantitatively the percentage of material released from the vesicles upon the addition of serum or Triton X-100 to vesicles. The percentage of vesicles remaining intact in vivo can also be monitored continuously by the present technique. In mice, the half-life of dipalmitoyl phosphatidylcholine-cholesterol vesicles after intraperitoneal injection was estimated to be 10-13 hr. The present study suggests that the vesicles remain intact in various tissues for extended periods, thereby allowing a slow release of the encapsulated material at those sites.