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 improv ed delivery system that could act as a locally targeted sustained-rele ase drug depot. This communication reports the first stage of the inve stigation and is focused on (a) the development of spectrophotometric assays for liposome-encapsulated and for free (aqueous soluble) and SS D, (b) on evaluation of the efficiency of encapsulation and kinetics o f drug release. DMSO containing 140 mM NH3 was found to be the best so lvent for dissolution of the liposomes and for determination of their SSD content. Peak absorption of liposome-originating SSD in this solve nt is at 263 nm with e(m) values of 23 x 10(3)-26 x 10(3). Peak absorp tion of SSD in aqueous solutions is at 254 nm with e(m) magnitudes var ying from 2 x 10(3) to 23 x 10(3), depending on the electrolytic compo sition of the system. Kinetic studies of drug release and separations by centrifugation and by gel-exclusion chromatography all indicate tha t the SSD in the liposomal system is distributed among three stares: e ncapsulated, soluble unencapsulated, and stable (unencapsulated) aggre gates that reside in the aqueous phase in which the liposomes are susp ended. The liposomal SSD systems were found to meet the essential requ irements 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 follo ws first-order kinetics, with half-life up to 24 hr and with sensitivi ty to the electrolytes in the system. It is concluded that SSD-liposom al systems are feasible, have potential benefits over treatment with f ree SSD, and merit further pursuit into providing local targeting.