Emerging nanomaterials with advanced drug delivery functions; focused on methotrexate delivery

This review focuses on therapeutic applications of various drug delivery nanovehicles encapsulated with the anti-cancer drug, methotrexate (MTX). Currently, a number of studies have been conducted to explore advanced chemotherapeutic systems with nonviral nanovehicles such as liposomes, polymeric micelles, polymersomes, solid lipids, dendrimers, porous metal and metal oxide particles, carbons with various nanostructures, and layered double hydroxides (LDHs). Out of various anticancer drugs, MTX was hybridized with those drug delivery nanovehicles not only to overcome its adverse effects, but also to induce advanced functions into those hybrid systems, such as enhanced solubility, controlled release, passive and active targeting, aimed to eventually enhance bioavailability of MTX. In particular, two dimensional LDHs are introduced rather in detail as one family of inorganic nanovehicles, since the therapeutic efficacies for MTX-LDHs have been systematically studied with in vivo orthotopic models, those which are clinically better correlated and therefore, more efficient to predict drug efficacy and toxicity than the standard one like xenograft model. Attempts are also made here to provide therapeutic results on chemically well defined MTX-LDH advanced drug delivery systems, such as their in vitro and in vivo targeting functions, biocompatibility and nanotoxicities and ability to overcome drug resistance. In addition, recent advances and challenges in advanced hybrid DDSs are discussed from the viewpoint of state-of-the-art nanomedicine.