Microemulsions combine the advantages of emulsions with those of nanocarriers, overcoming the stability problems of the former and providing facile scalable systems with compartments adequate for high drug loadings. Recently, microemulsions are gaining attention in the formulation of anticancer drugs not only for topical treatment, but also for systemic delivery as well as for the development of theranostic systems. The aim of this paper is two-fold. First, an updated review about general features, preparation, characterization and pharmaceutical applications, with a special focus on colorectal cancer, is provided. Second, a case study of formulation of methotrexate in microemulsions is presented. Various essential oils (menthol, trans-anethole, α-tocopherol) and surfactants (TPGS-1000, Maxemul 6112, Noigen RN-20) were investigated for the preparation of o/w microemulsions for the delivery of methotrexate, and the ability of methotrexate-loaded microemulsions to inhibit cancer cell growth was then evaluated. Disregarding the surfactants used, menthol and trans-anethole led to cytotoxic microemulsions, whereas α-tocopherol based-formulations induced cell proliferation. These findings highlight the role that the oily component may play in the efficacy and safety of the microemulsions.
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