Is stability a key parameter in the accumulation of phospholipid vesicles in tumors?
Phospholipid vesicle (liposome) stability in human plasma was determined using perturbed angular correlation (PAC) with 111In as the aqueous phase marker. Using compositions given in earlier tumor imaging studies, liposomes were made with either egg lecithin (EL) or distearoyl phosphatidylcholine (DSPC) as the dominant phospholipid. With fresh human plasma at 37 degrees C. EL vesicles lysed much more rapidly with survival half times being 7 hr at 6.7 mg lipid/ml plasma. DSPC liposomes had a half-time of 130 hr independent of lipid concentration. No lysis occurred with plasma previously stored for 1 wk at 5 degrees C. The addition of 143 USP units of heparin per 4.5 ml sample decreased both half-times by two orders of magnitude. We conclude that EL vesicles exhibit plasma survival times much shorter than those found with DSPC liposomes; this may preclude the former agents from having significant tumor accumulation in vivo.
D006207:Half-Life; D006493:Heparin; D006801:Humans; D066298:In Vitro Techniques; D007204:Indium; D008081:Liposomes / Q000008:administration & dosage / Q000097:blood*; D009369:Neoplasms / Q000097:blood*; D010713:Phosphatidylcholines; D011868:Radioisotopes; D013048:Specimen Handling
D008081:Liposomes; D010713:Phosphatidylcholines; D011868:Radioisotopes; D007204:Indium; D006493:Heparin; C010942:1,2-distearoyllecithin