The high probability (13%) of women developing breast cancer in their lifetimes in America is exacerbated by the emergence of multidrug resistance after exposure to first-line chemotherapeutic agents. Permeation glycoprotein (P-gp)-mediated drug efflux is widely recognized as the major driver of this resistance. Initial in vitro and in vivo investigations of the co-delivery of chemotherapeutic agents and P-gp inhibitors have yielded satisfactory results; however, these results have not translated to clinical settings. The systemic delivery of multiple agents causes adverse effects and drug–drug interactions, and diminishes patient compliance. Nanocarrier-based site-specific delivery has recently gained substantial attention among researchers for its promise in circumventing the pitfalls associated with conventional therapy. In this review article, we focus on nanocarrier-based co-delivery approaches encompassing a wide range of P-gp inhibitors along with chemotherapeutic agents. We discuss the contributions of active targeting and stimuli responsive systems in imparting site-specific cytotoxicity and reducing both the dose and adverse effects.

Nano-medicine is the fastest growing field in pharmaceutical industry today. However, there still exist several hurdles preceding its clinical translation. This review provides insights on the guidelines for nanomaterials provided by the US-FDA (United States Food and Drug Administration), various approval pathways and also addresses the lacunae between academic research, pharmaceutical industry and US-FDA through an attempt to overcome the hurdle to its clinical translation. We have also emphasized various ways to overcome the described barriers which will provide the readers a brief understanding over the critical aspects where the scope of the guidelines may need to be revisited in order to exhibit their successful clinical translation from academic research to commercial feasibility.