colistin and cholesteryl-sulfate

The potential use of liposomes for the pulmonary delivery of colistin has been hindered by their phospholipid membrane permeability resulting in a very low entrapment of colistin in the liposomes. To increase the entrapment capacity of colistin in liposomes, the anionic lipid sodium cholesteryl sulfate (Chol-SO4

Topics: Animals; Anti-Bacterial Agents; Cholesterol Esters; Colistin; Drug Carriers; Drug Compounding; Liposomes; Mice, Inbred Strains; Microscopy, Electron, Transmission; Particle Size; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Static Electricity; Surface Properties; Time Factors; Tissue Distribution

Potential use of liposome for polycationic colistin is hindered by their phospholipid membrane permeability. In this study, liposomes were modified with sodium cholesteryl sulphate (Chol-SO4(-)) for improving the colistin loading by enhancing the colistin-bilayer electrostatic attraction. We have evaluated two liposomes: colistin-entrapped liposome of Chol-SO4(-) (CCL) and coated Chol-SO4(-)/colistin complex liposome (CCCL). In comparison with CCL which formed large aggregates at Chol-SO4(-)/colistin charge ratio below 2:1, CCCL showed a smaller size less dependent on the charge ratio, probably arising from more colistin entrapped on the inner leaflet of bilayer. Both liposomes exhibited significantly increased entrapment efficiency as compared with the liposome without Chol-SO4(-). But colistin released upon dilution, implying free transfer of colistin through bilayers. Pharmacokinetics results showed the approximately four-fold increase in the plasma AUC0-8 h for CCCL and CCL as compared with colistin solution, showing potential benefit for infectious target localisation by prolonging the systemic circulation of colistin.

Topics: Administration, Intravenous; Animals; Cholesterol Esters; Colistin; Liposomes; Male; Rats; Rats, Sprague-Dawley; Static Electricity