ABSTRACT
This chapter is by design limited in scope. To review the entirety of animal and human experience would fill many volumes, and require an immense multidisciplinary effort. First, we limit this discussion to parenteral liposomes used in conventional drug delivery applications. We, further, restrict ourselves to products that have been completely through the drug development process: from preclinical screening in animals, through the normal phases of clinical trials, culminating in large, randomized registrational trials, and subsequent approvals. Examined from this perspective, we explore the question-what information on ultimate clinical outcome could be adduced from earlier (or even later performed) animal experiments. Do the therapeutic index enhancements, realized either on the safety/toxicity or efficacy aspects, that were anticipated during early drug development, translate into the ultimate product profile? This is not always as straightforward as one
might imagine. One does not design, and indeed cannot always ethically design, clinical trials as would be done from a simple scientific approach. Specifically, a liposomal drug is rarely compared directly and in the samemanner to a free drug given in the same way. Nevertheless, some lessons can be learned from the products that have thus far made it to regulatory approval and commercialization. These lessons are important in the consideration for development of a new generation of liposomal therapeutics, and in building reasonable expectations on what can be learned in nonclinical programs.
