Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes

Journal Article · Fri May 01 04:00:00 EDT 1987 · Invest. Ophthalmol. Visual Sci.; (United States)

OSTI ID:6331699

Barza, M; Stuart, M; Szoka, F Jr

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 /sup 125/I and contained /sup 51/Cr-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; /sup 51/Cr-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 /sup 51/Cr-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 /sup 51/Cr-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 /sup 51/Cr-EDTA and liposomes (/sup 125/I label) had a shorter half-life in infected than in normal eyes. Encapsulation of /sup 51/Cr-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.

• Research Organization: Tufts-New England Medical Center Hospitals, Boston, MA
• OSTI ID: 6331699
• Journal Information: Invest. Ophthalmol. Visual Sci.; (United States), Journal Name: Invest. Ophthalmol. Visual Sci.; (United States) Vol. 5; ISSN IOVSD
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHELATING AGENTS
CHEMICAL COMPOSITION
CHOLESTEROL
CHROMIUM 51
CHROMIUM ISOTOPES
CLEARANCE
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
EDTA
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HALF-LIFE
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE COMPOUNDS
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIPOSOMES
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
PHARMACOLOGY
RABBITS
RADIOISOTOPES
SENSE ORGANS DISEASES
SIZE
STEROIDS
STEROLS
TISSUE DISTRIBUTION
VERTEBRATES