Ratiometric drug delivery using non-liposomal nanocarriers as an approach to increase efficacy and safety of combination chemotherapy

The observation that different drug ratios of the same drug combination can lead to synergistic or antagonistic effects when tested against the same cancer cell line in vitro gave rise to a new trend, the ratiometric delivery. This strategy consists of co-encapsulating a specific synergistic ratio of a drug combination into a nanocarrier so that synergism observed in vitro will be faithfully translated to in vivo, optimizing combination therapy. In this review we focus on how to quantify synergism in vitro, followed by how this affected the evolution of nanocarriers culminating in the ratiometric delivery, and finally we summarize the results of the non-liposomal formulations that were built upon this concept.