Co-delivery systems: hope for clinical application?

Cancer is a multidimensional and challenging disease to handle. Current statistics reveal that we are far from satisfying cancer treatment. Taking advantage of different therapeutic agents that affect multiple pathways has been established as highly productive. Nevertheless, owing to several hindrances to conventional combination therapy, such as lack of tumor targeting, non-uniform pharmacokinetic of the combined drugs, and off-target side effects, it is well documented that this treatment approach is unlikely to address all the difficulties observed in monotherapy. Co-delivery systems could enhance the therapeutic efficacy of the combination therapy by targeting cancer cells and improving the pharmacokinetic and physicochemical properties of the therapeutic agents. Nevertheless, it seems that present knowledge in responding to the challenges in cancer treatment is still inadequate and far from optimal treatment, which highlights the urgent need for systematic studies direct to identify various aspects of co-delivery systems. Accordingly, to gather informative data, save time, and achieve superior results, the following steps are necessary: (1) implementing computational methods to predict drug-drug interactions (DDIs) in vitro and in vivo, (2) meticulous cancer studies at the cellular and molecular levels to obtain specific criteria for selecting preclinical and clinical models, (3) extensive physiological and pharmacokinetic study of nanocarriers behavior in preclinical models, and (4) finding the optimal formulation and analyzing its behavior in cellular and animal models facilitates bridging in vivo models to clinical trials. This review aims to deliver an overview of co-delivery systems, rationales, and suggestions for further studies in this field.