Liposomal entrapment of suramin(II): interaction of suramin with phospholipids of various chain lengths.
Previously, we reported that the entrapment of suramin in dipalmitoylphosphatidylcholine (DPPC, C16) multilamellar liposomes ranged from 25% to 65% and the addition of 30-50 mol% cholesterol (CHL) greatly reduced entrapment. Entrapment of small molecules similar to suramin, disodium 1,5-naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthalenedisulfonic acid (1.2%), were very low. In the present study, the entrapment and interaction of suramin with dilauroylphosphatidylcholine (DLPC, C12), dimyristoylphosphatidylcholine (DMPC, C14), and distearoylphosphatidylcholine (DSPC, C18) liposomes was investigated. DLPC and DMPC showed 2-3-fold higher entrapment percentages (95.1% and 74.2%, respectively) than DPPC (37%). However, the entrapment with DSPC (29%) was about 25% lower than DPPC. Adding 50 mol% cholesterol greatly reduced suramin entrapment for all phospholipids. The entrapment of polysulfonated dyes such as Evans blue, Direct blue 1, or Trypan blue, which are structurally similar to suramin, was found to be in the same order of DLPC > DMPC > DPPC > DSPC. Differential scanning calorimetry of aqueous dispersions of DLPC and DMPC with suramin showed more apparent interaction than for DPPC and DSPC. These results suggest that a large portion of the associated suramin and other polysulfonated compounds results from binding to the surface of the phospholipid bilayer or intercalation into the liposomal bilayer. The phospholipid chain length effect on entrapment may be due to the lower net van der Waals interaction between hydrocarbon chains for shorter acyl chains which also increases the bilayer intermolecular spacing. Such effects could then increase the ability of suramin to interact with individual phospholipid molecules.
Chang
H C
HC
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Flanagan
D R
DR
D001391:Azo Compounds / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004396:Coloring Agents; D005070:Evans Blue; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; D013498:Suramin / Q000008:administration & dosage* / Q000737:chemistry; D013696:Temperature; D014343:Trypan Blue
D001391:Azo Compounds; D004396:Coloring Agents; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; C009000:pontamine sky blue; D005070:Evans Blue; D013498:Suramin; D014343:Trypan Blue