CHARACTERIZATION OF BIOTINYLATED LIPOSOMES FOR IN-VIVO TARGETING APPLICATIONS

Liposomes containing monosialoganglioside (G(M1)) or polyethylene glyc ol (PEG) lipid derivatives have prolonged circulation in the blood. Th is favours liposome extravasation to tumour sites. In this report it i s shown that inclusion of G(M1), PEG550-DPPE or PEG2000-DPPE in liposo mes containing biotin-DPPE significantly diminished the ability of ves icles to bind to streptavidin in vitro. Steric inhibition due to the b ulky head group of these lipids was least for biotin-DPPE liposomes co ntaining G(M1). Biodistribution studies in C26 tumour-bearing mice sho wed that G(M1)-liposomes containing small amounts of biotin-DPPE have long circulation life-times in the blood. Using fluorescent microscopi c techniques, liposomes containing both G(M1) and biotin-DPPE were det ected within extra-vascular spaces in tumours. In addition it was show n that biotin-DPPE in G(M1)-liposomes bound streptavidin in situ. Thes e results suggest that G(M1)-liposomes containing biotin-DPPE have pot ential use as diagnostic or therapeutic reagents in pre-targeting appl ications dependent on the high-affinity interaction of biotin with str eptavidin.