ABSTRACT
A quarter century has passed since Yatvin et al. (1) suggested that low pH-sensitive liposomes (Scheme 1) might provide a means to preferentially localize drug release in a tumor. They made this suggestion based upon their insight that the pH in the tumor environment is 0.2 to 0.5 pH units more acidic than in the blood or in normal tissue. This novel suggestion was one of the earliest descriptions of a liposome that would change its properties in the presence of a discrete biological environment. Since then, advances in liposome technologies have solved many of the problems faced by the conventional liposomal carriers, such as the loading efficiency, contents retention, plasma stability, and circulation lifetime. These advances accelerated the transfer of liposome-encapsulated low-molecular-weight drugs from
Scheme 1
the laboratory to the clinic (2). However, bioresponsive liposomes have not yet provided a clear advantage for the delivery of drugs, either low or high molecular weight, in animals. For instance, in vivo liposomal delivery of macromolecular therapeutics such as DNA, RNA, and proteins remains problematic; many groups believe success in this challenge requires more sophisticated systems, such as bioresponsive liposomes, to transfer these macromolecules across the subcellular barriers to reach their intracellular target site.
