Lipid Based Nanoparticles as Inherent Reversing Agents of Multidrug Resistance in Cancer.

Abstract

Multidrug resistance in cancer is the ability of a cancer cell to resist treatment with a wide range of structurally and functionally dissimilar chemotherapeutics. The resistant phenotype could arise in response to several cellular changes that ultimately result in a decrease in intracellular drug accumulation (or effectiveness), either by limiting cellular drug entry, or by expulsion of those molecules that have made it into the cell. Both blocking drug cellular entry and its expulsion are mostly brought about by the cell membrane. Several pharmaceutical excipients (mainly lipids, surfactants and amphililc copolymers) have been reported to reverse multidrug resistance by addressing cell membrane related changes resulting in low intracellular drug levels in resistant cells. These excipients are routinely used in the preparation of lipid based nanoparticles endowing inherent multidrug resistance reversing properties to these nanoparticles. In this review, cell membrane alterations resulting in multidrug resistance will be initially reviewed, followed by a discussion of the different types of lipid NPs and the potential held by the excipients used in their preparation in multidrug resistance reversal. Finally, a discussion on how lipid nanoparticles have been engineered and used in different occasions to enable multidrug resistance reversal is included. The superior role held by lipid nanoparticles in comparison to free excipients will be highlighted.