nanomaterials Review Recent Advances in Nanosystems and Strategies for Vaginal Delivery of Antimicrobials Giulia Chindamo , Simona Sapino * , Elena Peira , Daniela Chirio and Marina Gallarate   Citation: Chindamo, G.; Sapino, S.; Peira, E.; Chirio, D.; Gallarate, M. Recent Advances in Nanosystems and Strategies for Vaginal Delivery of Antimicrobials. Nanomaterials 2021, 11, 311. https://doi.org/10.3390/ nano11020311 Academic Editor: László K˝ orösi Received: 23 December 2020 Accepted: 22 January 2021 Published: 26 January 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 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/). Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; giulia.chindamo@unito.it (G.C.); elena.peira@unito.it (E.P.); daniela.chirio@unito.it (D.C.); marina.gallarate@unito.it (M.G.) * Correspondence: simona.sapino@unito.it; Tel.: +39-011-670-6800 Abstract: Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided. Keywords: vaginal infections; antimicrobials; drug delivery systems; nanocarriers; local therapies 1. Introduction The vagina is a muscle-membranous canal that extends from the vulva to the cervix. The wall of the vagina includes different layers: an inner mucosal tissue, consisting of a stratified squamous epithelium, a middle smooth muscle layer made of longitudinal and circular fibers, an external coat of connective tissue, and the peritoneum [1]. The vagina is involved in several functions such as sexual functions, but also in active immunologic and anatomically mediated processes essential for maintaining a microenvironment ideal for “normal” bacteria [2]. In particular, many studies have demonstrated that several immune- related cells and receptors are present in the vagina, helping the microbial environment. There are five major types of vaginal microbiota, known as community state types (CSTs). In four of these (CST-I, -II, -III, -V), Lactobacillus spp. is the predominant species; CST-IV, instead, is composed of a mixture of several facultative anaerobes, including Gardnerella, Atopobium, and Prevotella. The frequency of these CSTs is different according to the ethnic backgrounds. Alterations in normal composition and functions of vaginal flora are involved in the development of several vaginal diseases such as bacterial, fungal, and viral vaginosis and can also increase the risk of acquiring sexually transmitted infections such as HIV, as demonstrated by some studies [3]. Female reproductive tract-related diseases to (FRT) affect more than 10 million people each year. Their symptoms often include itching, burning, pain, and dyspareunia, and are responsible for significant distress for patients [4]. Nanomaterials 2021, 11, 311. https://doi.org/10.3390/nano11020311 https://www.mdpi.com/journal/nanomaterials