Liposome-encapsulated silver sulfadiazine (SSD) for the topical treatment of infected burns: thermodynamics of drug encapsulation and kinetics of drug release.
Liposomes encapsulating silver sulfadiazine (SSD), the drug of choice for topical treatment of infected burns, are investigated as an improved delivery system that could act as a locally targeted sustained-release drug depot. This communication reports the first stage of the investigation and is focused on (a) the development of spectrophotometric assays for liposome-encapsulated and for free (aqueous soluble) and SSD, (b) on evaluation of the efficiency of encapsulation and kinetics of drug release. DMSO containing 140 mM NH3 was found to be the best solvent for dissolution of the liposomes and for determination of their SSD content. Peak absorption of liposome-originating SSD in this solvent is at 263 nm with em values of 23 x 10(3)-26 x 10(3). Peak absorption of SSD in aqueous solutions is at 254 nm with em magnitudes varying from 2 x 10(3) to 23 x 10(3), depending on the electrolytic composition of the system. Kinetic studies of drug release and separations by centrifugation and by gel-exclusion chromatography all indicate that the SSD in the liposomal system is distributed among three states: encapsulated, soluble unencapsulated, and stable (unencapsulated) aggregates that reside in the aqueous phase in which the liposomes are suspended. The liposomal SSD systems were found to meet the essential requirements of high-efficiency encapsulation and sustained drug release. Encapsulation efficiencies of > 80% at 10 mM lipid, reaching up to 95% at 100 mM lipid, were obtained. The release of encapsulated SSD follows first-order kinetics, with half-life up to 24 hr and with sensitivity to the electrolytes in the system. It is concluded that SSD-liposomal systems are feasible, have potential benefits over treatment with free SSD, and merit further pursuit into providing local targeting.
Lichtenstein
A
A
Department of Biochemistry, Tel Aviv University, Israel.
Margalit
R
R
D002056:Burns / Q000188:drug therapy*; D002850:Chromatography, Gel; D004337:Drug Carriers; D007700:Kinetics; D008081:Liposomes; D012837:Silver Sulfadiazine / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D012997:Solvents; D013057:Spectrum Analysis; D013816:Thermodynamics; D014946:Wound Infection / Q000188:drug therapy*
D004337:Drug Carriers; D008081:Liposomes; D012997:Solvents; D012837:Silver Sulfadiazine