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  • Title: Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes.
    Author: Barza M, Stuart M, Szoka F.
    Journal: Invest Ophthalmol Vis Sci; 1987 May; 28(5):893-900. PubMed ID: 3106257.
    Abstract:
    We investigated the influence of size and lipid composition on the pharmacokinetic behavior of liposomes and their contents in the rabbit eye. Small and large unilamellar vesicles (SUV and LUV), prepared with and without cholesterol in the membrane, were injected intravitreally in rabbits. The vesicles were labelled with 125I and contained 51Cr-EDTA in the aqueous compartment. The mode of elimination of the vesicles from the vitreous humor is uncertain but may be via the anterior route; 51Cr-EDTA, like gentamicin, probably is eliminated by the anterior route. The rate of clearance of the lipid label appeared to be related to the size but not to the cholesterol content of the liposomes. Liposome-encapsulation prolonged the half-life of 51Cr-EDTA by up to 11-fold in the vitreous humor of normal eyes. The prolongation was greatest with cholesterol-containing vesicles, presumably because these are most stable, and was somewhat greater with large than with small vesicles. For SUV and LUV, the rate of elimination of 51Cr-EDTA from the normal eye was determined mainly by the rate of leakage from the liposomes, whereas for SUV-cholesterol and LUV-cholesterol, it was determined mainly by the rate of clearance of the liposomes themselves. Both 51Cr-EDTA and liposomes (125I label) had a shorter half-life in infected than in normal eyes. Encapsulation of 51Cr-EDTA prolonged its half-life by up to sevenfold in infected eyes; the effect was greatest with cholesterol-containing vesicles. These results suggest that both the structure of the liposome and the state of the eye may markedly affect the pharmacokinetic behavior of intravitreal liposomes.
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