Lyophilization and rehydration of polymer-coated lipid vesicles containing a lipophilic chelator in the presence of sucrose: labeling with 99mTc and biodistribution studies.
In this paper we describe studies of the effect of lyophilization and rehydration of polymer-coated lipid vesicles bearing a lipophilic surface chelator upon subsequent labeling with technetium-99m and in vivo biodistribution behavior. Unilamellar vesicles of average diameter 100 nm were prepared containing 2 mol% of the lipophilic chelator phosphatidylethanolamine-diethylenetriaminetetraacetic acid (PE-DTTA) and either 0 or 3 mol% of the lipid-polymer conjugate, dipalmitoyl-phosphatidyl-ethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG) in 0.9% sodium chloride to which was added varying amounts of sucrose to a final concentration of 100-500 mM. The size of the vesicles in sucrose was determined before lyophilization and after rehydration and the effect of sucrose on the ability to label the vesicles with pertechnetate in the presence of stannous chloride was determined. Biodistribution studies were done in rabbits with vesicles before lyophilization and after rehydration in order to determine whether the rate of clearance from the blood pool was affected by the lyophilization/rehydration procedure. Results demonstrate that vesicles containing PE-DTTA and without PE-MPEG can be lyophilized and rehydrated with no change in average size or size distribution so long as the external sucrose concentration is greater than approx. 250 mM. When PE-MPEG is also present in the membrane the average vesicle size increases from approx. 140 to 200 nm, consistent with vesicle fusion. However, this small change in vesicle size makes no difference to the resulting circulation half-life (approximately 2 h at a lipid dose of approximately 10 mumol/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Szucs
M
M
Department of Radiology, University of British Columbia, Vancouver, Canada.
Tilcock
C
C
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D002614:Chelating Agents; D004337:Drug Carriers; D005612:Freeze Drying; D006801:Humans; D008081:Liposomes; D008657:Metabolic Clearance Rate; D004369:Pentetic Acid / Q000031:analogs & derivatives; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D011817:Rabbits; D013395:Sucrose; D013667:Technetium / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D014867:Water
D002614:Chelating Agents; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014867:Water; C060068:diethylenetriaminetetraacetic acid; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D011092:Polyethylene Glycols; D013395:Sucrose; D013667:Technetium; D004369:Pentetic Acid; C028210:monomethoxypolyethylene glycol