ABSTRACT

Stabilization of liposomes by freeze-drying has been intensively investigated over the past two decades, since the initial reports appeared (1-6), which led to rapid adoption in the commercial arena. In fact, Ambisome, a liposomebased product for treatment of systemic fungal infections, has been delivered as a freeze-dried product since its first approval for use in the United Kingdom in 1991. Since those early reports, freeze-dried liposomes have been nebulized for use as an aerosol (7-10), sterilized by gamma radiation (11); the technology has been applied to cross-linked (12) and polyethyleneglycoxylated complexes (13,14); and stability of freeze-dried liposomes has been studied in several contexts (15-17). Investigations on freeze-drying have established the fundamental principles underlying the process, although, as we will discuss in this review, much is still to be learned about the mechanism.