LIPOSOMAL ENTRAPMENT OF SURAMIN

The liposomal entrapment of suramin and similar compounds in phospholi pid vesicles was examined. For dipalmitoylphosphatidylcholine (DPPC) l iposomes, entrapment percentages ranged from 25 to 65% with 3-25 mM ph ospholipid for aqueous solutions containing 0.07 mM of suramin. Incorp oration of 30-50 mol % cholesterol (CHL) into DPPC liposomes reduced t he percentage suramin entrapment. Addition of positively-charged stear ylamine (5 mol%) to DPPC/CHL liposomes increased the entrapment from 2 .3% to 30.3%. Entrapment was not affected by the incorporation of nega tively-charged phosphatidylglycerol into DPPC/CHL liposomes. When the amount of suramin was increased from 0.07 to 0.7 mM, the entrapment pe rcentage decreased from 37% to 11% when DPPC was held constant at 6 mM . The entrapment of 0.07 mM Evans blue, a molecule similar in structur e to suramin, was 51.6% in DPPC liposomes for 6 mM phospholipid. The e ntrapment percentage, however, decreased by about 50% when incorporate d into 7:3(DPPC/ CHL) liposomes. The liposomal entrapment of disodium 1,5-naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthale nedisulfonic acid (1.2%) was very low compared to that of suramin or E vans blue. Differential scanning calorimetry studies of suramin and an aqueous dispersion of DPPC showed an apparent interaction between the m. These observations suggest that a significant portion of the entrap ped suramin results from binding of suramin to the surface of or inter calation into the liposomal bilayer. Surface binding or intercalation into the phospholipid bilayer may be attributed to both ionic and hydr ophobic interactions. The ionic interaction would arise from the suram in sulfonate groups associating with the cationic choline portion of t he phospholipid. The hydrophobic interaction would arise from the cent ral portion of the suramin molecule associating with the phospholipid fatty acid chains.