Microemulsions and Nanoemulsions in Skin Drug Delivery

Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic dispersions of two nonmiscible liquids (oil and water), significant differences are encountered between microemulsions and nanoemulsions. Microemulsions are thermodynamically stable o/w emulsions of mean droplet size approximately 100–400 nm, whereas nanoemulsions are thermodynamically unstable o/w emulsions of mean droplet size approximately 1 to 100 nm. Their inner oil phase allows the solubilization of lipophilic drugs, achieving high encapsulation rates, which are instrumental for drug delivery. In this review, the importance of these systems, the key differences regarding their composition and production processes are discussed.

While most of the micro/nanoemulsions on the market are held by the cosmetic industry to enhance the activity of drugs used in skincare products, the development of novel pharmaceutical formulations designed for the topical, dermal and transdermal administration of therapeutic drugs is being considered. The delivery of poorly water-soluble molecules through the skin has shown some advantages over the oral route, since drugs escape from first-pass metabolism; particularly for the treatment of cutaneous diseases, topical delivery should be the preferential route in order to reduce the number of drugs used and potential side-effects, while directing the drugs to the site of action. Thus, nanoemulsions and microemulsions represent versatile options for the delivery of drugs through lipophilic barriers, and many synthetic and natural compounds have been formulated using these delivery systems, aiming to improve stability, delivery and bioactivity. Detailed information is provided concerning the most relevant recent scientific publications reporting the potential of these delivery systems to increase the skin permeability of drugs with anti-inflammatory, sun-protection, anticarcinogenic and/or wound-healing activities. The main marketed skincare products using emulsion-based systems are also presented and discussed.

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About this article: Souto, E.B.; Cano, A.; Martins-Gomes, C.; Coutinho, T.E.; Zielińska, A.; Silva, A.M. Microemulsions and Nanoemulsions in Skin Drug Delivery. Bioengineering 2022, 9, 158. https://doi.org/10.3390/bioengineering9040158

Conclusions
The skin is definitely a very promising route for drug administration and delivery. The ability to release drugs into the bloodstream at constant concentration levels, coupled with its high application area, the exemption of the first-pass effect and application comfort, make it the route of choice. Both microemulsions and nanoemulsions are carriers able to act as permeation/penetration enhancers through the skin due to the characteristics they bring together, allowing to overcome the barrier of the Stratum corneum. They may also increase the liposolubility of hydrophilic drugs, because a more nonpolar chain can be added to its more polar side, which gives ambivalence to molecules with bioavailability problems. The same happens with lipophilic substances, so that their more nonpolar side is added to a more polar chain. Microemulsions and nanoemulsions have similar macroscopic characteristics.

Although they are microemulsions, they have a droplet size smaller than that of nanoemulsions, which can cause some confusion. However, what distinguishes nanoemulsions is their kinetic behavior, conferred by the Brownian motion of the particle. Microemulsions have a high thermodynamic stability, making their shelf life longer compared to classic emulsions. On the other hand, despite having unstable thermodynamics, nanoemulsions have kinetic stability, which makes them resistant to degradation problems. These characteristics make these systems advantageous in the preservation of drugs, so that they remain in good condition until the moment of application. The high thermodynamic stability, as well as the kinetics, make these systems able to increase the permeation capacity in the skin and the drug’s sharing quotient, which promotes a good ability to overcome transdermal barriers. Both the behavior of these systems and the components of which they are made make these systems great promoters of skin permeation, which makes them good vehicles for transdermal drug delivery.

The extensive study of these systems gave rise to a set of production methods, with different characteristics chosen according to the availability of the laboratory and the properties of the molecules to be transmitted. It should be noted that in the case of nanoemulsions, it is possible to produce systems capable of successfully increasing the bioavailability of drugs that are poorly soluble in hydrophilic and lipophilic media, which can be a good solution to the problems faced by many drugs on the market. The existence of spontaneous production methods is of great value, especially in periods of resource containment, so there is a significant reduction in energy costs as well as high-cost machinery. These methods can be very advantageous in the case of large-scale production. However, it would be important to conduct further comparative studies between microemulsion and nanoemulsions system, in order to distinguish them unequivocally, which is the best method for application to the skin. This gap is due to the fact that they are still very novel in the scientific world.