Incorporation of new amphiphilic perfluoroalkylated bipyridine platinum and palladium complexes into liposomes: stability and structure-incorporation relationships.
New perfluoroalkylated side-chain (formed by a perfluoroalkyl tail grafted onto a hydrocarbon spacer) bipyridine complexes of platinum, palladium and their hydrocarbon analogs, when dispersed in aqueous solutions in the presence of egg yolk phospholipids (EYP), are incorporated into EYP vesicles. Most complexes retain their chemical and structural integrity when entrapped into liposomes, thermally sterilized under the FDA norms and stored for 3 months at 25 degrees C. All complex/liposome preparations consist mainly of small unilamellar vesicles (size less than 100 nm) together with a population of larger uni- or multilamellar vesicles (100 to 230 nm). These preparations are remarkably stable with respect to particle size and size distribution evolution and complex leakage: no precipitate of drug was detected even after 7 months of storage at 25 degrees C. The impact of the perfluoroalkyl tail and of the other structural features of the complexes on their incorporation efficiency into EYP liposomes is assessed. A high fluorophilic character (long perfluoroalkyl tail), when tempered by an equally lipophilic one (long hydrocarbon spacer) is not detrimental to the incorporation efficiency of a perfluoroalkylated drug into hydrocarbon vesicles. This incorporation efficiency is considerably improved by the introduction of a double bond between the perfluoroalkyl tail and the hydrocarbon spacer, forming the bipyridine side-chains.
Garelli
N
N
Laboratoire de Chimie Moléculaire, CNRS, Université de Nice-Sophia Antipolis, France.
Vierling
P
P
D004337:Drug Carriers; D004355:Drug Stability; D005466:Fluorocarbons / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry
D004337:Drug Carriers; D005466:Fluorocarbons; D008081:Liposomes; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D011725:Pyridines; D010165:Palladium