ACCUMULATION OF PROTEIN-COATED LIPOSOMES IN AN EXTRAVASCULAR SITE - INFLUENCE OF INCREASING CARRIER CIRCULATION LIFETIMES

Citation
Sa. Longman et al., ACCUMULATION OF PROTEIN-COATED LIPOSOMES IN AN EXTRAVASCULAR SITE - INFLUENCE OF INCREASING CARRIER CIRCULATION LIFETIMES, The Journal of pharmacology and experimental therapeutics, 275(3), 1995, pp. 1177-1184
Citations number
36
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
275
Issue
3
Year of publication
1995
Pages
1177 - 1184
Database
ISI
SICI code
0022-3565(1995)275:3<1177:AOPLIA>2.0.ZU;2-A
Abstract
The primary objective of this work was to test whether increased blood levels and circulation lifetimes result in increased passive targetin g of protein-coated liposomal drug carriers. The system used to evalua te this was based on i.v. injection of 100 nm of distearoyl phosphatid ylcholine/cholesterol liposomes with covalently bound streptavidin. Th e circulation lifetime of these liposomes was increased by procedures that involved blockade of liposome uptake by phagocytic cells in the l iver and/or the incorporation of a poly(ethylene glycol)-modified phos pholipid [poly(ethylene glycol)(2000)-modified distearoyl phosphatidyl ethanolamine]. Blockade of liver phagocytic cells with a low predose ( 2 mg/kg of drug) of liposomal doxorubicin increased the circulation ha lf-life of the streptavidin liposomes from less than 1 hr to greater t han 3 hr. A further 2-fold increase in circulating half-life (to appro ximately 7.5 hr) was achieved by using liposomes with 2 mole% of poly( ethylene glycol)(2000)-modified phosphatidylethanolamine. In combinati on with RES blockade, the circulation lifetimes of poly(ethylene glyco l)phosphatidylethanolamine containing streptavidin liposomes could be increased to greater than 12 hr. The ability of these liposomes to mov e from the plasma compartment to an extravascular compartment was meas ured by using the peritoneal cavity as a convenient, accessible, extra vascular site. The tendency for liposomes to accumulate in this site w as not, however, clearly dependent on circulating blood levels. Compar able levels of liposomes in the peritoneal cavity were achieved when u sing systems that exhibited significantly different circulation lifeti mes.