In this review, we deal with the formation and application of biocompatible water-in-oil microemulsions commonly known as reverse micelles (RMs). These RMs are extremely important to facilitate the dissolution of hydrophilic and hydrophobic compounds for biocompatibility in applications in drug delivery, food science, and nanomedicine. The combination of two wisely chosen types of compounds such as biocompatible non-polar solvents and ionic liquids (ILs) with amphiphilic character (surface-active ionic liquids, SAILs) can be used to generate organized systems that perfectly align with the Green Chemistry concepts. Thus, we describe the current state of SAILs (protic and aprotic) to prepare RMs using non-polar but safe solvents such as esters derived from fatty acids, among others. Moreover, the use of the biocompatible solvents as the external phase in RMs and microemulsions/nanoemulsions with the other commonly used biocompatible surfactants is detailed showing the diversity of preparations and important applications. As shown by multiple examples, the properties of the RMs can be modified by changes in the type of surfactant and/or external solvents but a key fact to note is that all these modifications generate novel systems with dissimilar properties. These interesting properties cannot be anticipated or extrapolated, and deep analysis is always required. Finally, the works presented provide valuable information about the use of biocompatible RMs, making them a green and promising alternative toward efficient and sustainable chemistry.

Imim–DEHP, a versatile protic IL-like surfactant to formulate aqueous RMs in biocompatible non-polar solvents.

In the last decade, the nature of the nonpolar solvents that can be part of reverse micelles (RMs) has been the topic of several investigations to improve their applications. In this sense, the hydrolysis of 1-naphthyl phosphate catalyzed by the enzyme alkaline phosphatase (AP) was used as a probe to investigate the effect of the change of the external solvent on RMs formulated with the anionic surfactant sodium diethylhexyl sulfosuccinate (AOT). As external nonpolar solvents, two biocompatible lipophilic esters, isopropyl myristate and methyl laurate, and the traditional nonpolar solvents, n-heptane and benzene, were used. The results were compared among the RMs investigated and with the reaction in homogeneous media. Thus, the effect of the nanoconfinement as well as the impact of the replacement of a conventional external nonpolar solvent by biocompatible solvents were analyzed. The results indicate that the catalytic efficiency in the AOT RMs is larger than that in homogeneous media, denoting a different hydration level over the AP enzyme, which is directly related to the different degrees of nonpolar solvent penetration to the RM interface. Our findings demonstrated that toxic solvents such as n-heptane and benzene can be replaced by nontoxic ones (isopropyl myristate or methyl laurate) in AOT RMs without affecting the performance of micellar systems as nanoreactors, making them a green and promising alternative toward efficient and sustainable chemistry.