CARBOPLATIN LIPOSOMES COATED WITH O-PALMITOYLPULLULAN - IN-VITRO CHARACTERIZATION

Encapsulation and stability of carboplafin in large unilamellar liposo mes (LW) of L-alpha egg phosphatidylcholine (PC), uncoated and coated with 0-palmitoylpullulan (OPP), were studied. Synthesized OPP was char acterized by infrared (IR) spectroscopy, revealing the existence of a covalent bond between the pullulan and palmitoyl groups, and by proton nuclear magnetic resonance (H-1-NMR) spectroscopy, allowing the calcu lation of the substitution degree of palmitoyl groups in pullulan (0.4 %). Moreover, encapsulated carboplatin does not change the fluorescenc e polarization of either 1,6-diphenyl-1,3,5-hexatriene (DPH) or 3-[p-( 6-phenyl-1,3,5-hexalrienyl]phenylp acid (DPH-PA), suggesting that this drug does not modify the membrane lipid organization either in the bi layer core or in the outer domains, as monitored by DPH and by DPH-PA, respectively. Carboplatin encapsulation in LW and their stability see m to be simultaneously improved by hydration in a medium without chlor ide ions and with an ionic strength equivalent to 0.6% NaCl. Additiona lly, it is shown that stability of carboplatin liposomes, as measured by the platinum remaining associated with liposomes (platinum latency) , is improved by coating with OPP, for an OPP/PC weight ratio of 3. Hi gher OPP/PC weight ratio values (e.g. 7.5) induce an opposite effect. (C) 1997 Elsevier Science B.V.