A Model Approach for Assessing Liposome Targeting

A procedure intended to facilitate characterization and optimization of liposomes designed for in uiuo tar-geting to sites outside the blood compartment is de-scribed. The approach is based on a model consisting of administering streptavidin liposomes intravenously to mice previously injected intraperitoneally or intra-tumorally with biotinylated multilamellar vesicles (MLVs). In uiuo targeting, therefore, is measured through the evaluation of streptavidin liposome accu-mulation and distribution within the site of MLV injec-tion. In uitro studies suggested that optimal binding would be achieved when streptavidin liposomes, prepared with 2 mol % polyethylene glycol-modified phospholipids (PEG-SA-LW), were incubated with multilamellar vesicles incorporating biotinoylamino-hexanoyl DSPE (BAH-MLV). In uiuo targeting studies were focused in three areas. The least stringent test determined PEG-SA-LW binding to biotinylated MLVs in the peritoneal cavity after ip administration and resulted in a 17-fold increase in binding of PEG-SA-LWs to MLVs within the peritoneal cavity 24 h after injection. Alternatively, a &fold increase in bind-ing to MLVs was achieved in animals when the PEG-SA-LWs were administered intravenously. The third approach consisted of iv administration of PEG-SA-L W s into mice bearing subcutaneous Lewis lung tu-mors that had been injected with either BAH-MLVs or, in a contralateral tumor, control MLVs. Under these conditions a 2-fold increase in tumor accumulation was achieved in tumors injected with the biotinylated MLVs. The results presented indicate that approaches designed to facilitate targeting of liposomal drugs to extravascular sites will result in little or no change in the capacity of these liposomes to accumulate pas-sively. D 1996 Academic Press, he. To whom correspondence should be addressed. Fax: (604) 822