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.