A methotrexate (MTX)-layered double hydroxide (LDH) hybrid have been developed as a drug delivery system, in which an anticancer drug, MTX, was intercalated into a 2-dimensional LDH nanovehicle to form a nanohybrid. According to the comparative cell viability studies between MTX only and its LDH nanohybrid on MTX sensitive and resistant cell culture lines, it was found that the MTX-LDH nanohybrid could bypass the MTX resistance and eventually inhibit cancer cell proliferation very effectively compared to free MTX, due to an enhanced permeability and retention effect of MTX-LDH nanoparticles even in dihydrofolate reductase-overexpressing MTX-resistant cells. This is definitely associated with the uptake mechanism via a clathrin-mediated endocytic pathway for the MTX-LDH nanohybrid particles, the same as for the LDH nanocarrier only, which is completely different from the cellular uptake mechanism for MTX only, the reduced folate carrier (RFC) and/or the folate receptor entries.

Focus here is placed on the pharmaceutical and biomedical applications of novel clay-drug hybrid materials categorized by methods of administration. Clay minerals have been used for many years as pharmaceutical and medicinal ingredients for therapeutic purposes. A number of studies have attempted to explore clay-drug hybrid materials for biomedical applications with desired functions, such as sustained release, increased solubility, enhanced adsorption, mucoadhesion, biocompatibility, targeting, etc. The present review attempts not only to summarize the state-of-the-art of clay-drug hybrid materials and their advantages, depending on the methods of administration, but also to deal with challenges and future perspectives of clay mineral-based hybrids for biomedical applications.

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130[emsp14]nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2[emsp14]hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.