Strategies for triggered drug release from liposomes: in search of "smart" lipids and "smart" triggers

Abstract

Long circulating liposomal drug carriers are widely used in experimental cancer therapy because they avoid excretion and benefit from the EPR-effect to accumulate at the tumor site while simultaneously limiting systemic exposure to the cytotoxic drug. New insights in lipid behavior have led to such stable carriers that despite increased accumulation, the unloading of the drug at the target site is very poor. This opens up a new challenge to trigger drug release at the target site, while still retaining most of the drug inside the carrier while it resides in the bloodstream. Liposomes are very suitable to design these kinds of triggered release systems, because of the diversity of lipids and versatility of lipid membranes. Triggers can be intrinsic, i.e.located at the tumor site, or applied from the outside. Intrinsic triggers such as the acidic environment at the tumor, or the increased expression of phospholipases, and applied triggers such as radiation, light or heat can destabilize the membranes of smartly designed liposomes. Creating a triggered release system will always be a trade-off between systemic stability and susceptibility to the trigger. However, sophisticated triggering systems, that combine a trigger with an advanced imaging system, can further optimize the efficacy of targeted triggered release.