Abstract: Hindawi Publishing Corporation International Journal of Biomaterials Volume 2016, Article ID 8043983, 15 pages http://dx.doi.org/10.1155/2016/8043983 Research Article Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin Romina Croci,1 Elisabetta Bottaro,2 Kitti Wing Ki Chan,3 Satoru Watanabe,3 Margherita Pezzullo,1 Eloise Mastrangelo,1,4 and Claudio Nastruzzi2 1 Department of Bioscience, University of Milan, 20133 Milan, Italy Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy 3 Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857 4 Institute of Biophysics, National Research Council, 20133 Milan, Italy 2 Correspondence should be addressed to Claudio Nastruzzi; nas@unife.it Received 22 December 2015; Revised 17 March 2016; Accepted 31 March 2016 Academic Editor: Rosalind Labow Copyright © 2016 Romina Croci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.