Pharmacokinetics of pegylated liposomal asODNs

摘要

We have set out to devleop a liposomal formulation of antisense oligodeoxynucleotides (asODNs) which maintains the entrapment efficiency of cationic liposomes, and also maintains suitable size and stability characteristics to be appropriate for i.v. administration. Liposomal asODNs which could circulate for extended periods may provide an advantageous pharmacokinetic (PK) profile suitable for both passive and active targeting to target tissues. In this paper we describe a liposomal asODN formulation which contains 25 mole percent cationic phospholipid, entraps approximately 85percent of added ODN, maintains a homogenous size distribution <200 nm, has minimal uptake into tissues of the RES and is able to circulate for extended times when injected i.v. into mice. This formulation represents an alternative to cationic lipid-ODN complexes, which are rapidly tkane up by RES tissues.