  Citation: Souto, E.B.; Cano, A.; Martins-Gomes, C.; Coutinho, T.E.; Zieli ´ nska, A.; Silva, A.M. Microemulsions and Nanoemulsions in Skin Drug Delivery. Bioengineering 2022, 9, 158. https://doi.org/ 10.3390/bioengineering9040158 Academic Editor: Ching-An Peng Received: 26 February 2022 Accepted: 1 April 2022 Published: 5 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). bioengineering Review Microemulsions and Nanoemulsions in Skin Drug Delivery Eliana B. Souto 1,2, * , Amanda Cano 3,4,† , Carlos Martins-Gomes 5,6,† , Tiago E. Coutinho 5,6 , Aleksandra Zieli ´ nska 7 and Amélia M. Silva 5,6, * 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal 2 REQUIMTE/UCIBIO, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal 3 Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona, 08007 Barcelona, Spain; acanofernandez@ub.edu 4 Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08007 Barcelona, Spain 5 Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal; camgomes@utad.pt (C.M.-G.); tcoutinho4@hotmail.com (T.E.C.) 6 Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal 7 Institute of Human Genetics, Polish Academy of Sciences, Strzeszy ´ nska 32, 60-479 Pozna ´ n, Poland; aleksandra.zielinska@igcz.poznan.pl * Correspondence: ebsouto@ff.up.pt (E.B.S.); amsilva@utad.pt (A.M.S.) † These authors contributed equally to this work. Abstract: Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic disper- sions 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 per- meability 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. Keywords: microemulsions; nanoemulsions; skin drug delivery; skin bioavailability 1. Introduction Transdermal delivery is a convenient form of drug administration, as it allows a con- trolled release of the drug with minimum side effects and a higher patient compliance rate. Bioengineering 2022, 9, 158. https://doi.org/10.3390/bioengineering9040158 https://www.mdpi.com/journal/bioengineering