A Safe-by-Design Approach for the Synthesis of a Novel Cross-Linked Hyaluronic Acid with Improved Biological and Physical Properties

first_pagesettingsOrder Article Reprints Open AccessArticle A Safe-by-Design Approach for the Synthesis of a Novel Cross-Linked Hyaluronic Acid with Improved Biological and Physical Properties by Sabrina Sciabica 1,†,Riccardo Barbari 1,†ORCID,Riccardo Fontana 2ORCID,Giovanni Tafuro 3,Alessandra Semenzato 4ORCID,Daniela Traini 5,6ORCID,Dina M. Silva 6,Larissa Gomes Dos Reis 6,Luisa Canilli 7,Massimo Terno 7,Peggy Marconi 2ORCID,Anna Baldisserotto 1,*ORCID,Silvia Vertuani 1,* andStefano Manfredini 1ORCID 1 Department of Life Sciences and Biotechnology, University of Ferrara, via L. Borsari 46, 44121 Ferrara, Italy 2 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, via Fossato di Mortara 64/B, 44121 Ferrara, Italy 3 Unired Srl, via Niccolò Tommaseo 69, 35131 Padova, Italy 4 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy 5 Macquarie Medical School, Faculty of Medicine, Health & Human Sciences, Macquarie University, Campus Macquarie Park, Sydney 2109, Australia 6 Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, Sydney 2037, Australia 7 Istituto Ganassini S.p.a., Via Carlo Boncompagni, 63, 20139 Milano, Italy * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. Pharmaceuticals 2023, 16(3), 431; https://doi.org/10.3390/ph16030431 Received: 20 February 2023 / Revised: 7 March 2023 / Accepted: 9 March 2023 / Published: 11 March 2023 (This article belongs to the Special Issue Novel Applications of Natural Polysaccharides for Pharmaceuticals) Download Browse Figures Versions Notes Abstract Hyaluronic acid (HA) is a polymer with unique biological properties that has gained in interest over the years, with applications in pharmaceutical, cosmetic, and biomedical fields; however, its widespread use has been limited by its short half-life. Therefore, a new cross-linked hyaluronic acid was designed and characterized using a natural and safe cross-linking agent, such as arginine methyl ester, which provided improved resistance to enzymatic action, as compared to the corresponding linear polymer. The antibacterial profile of the new derivative was shown to be effective against S. aureus and P. acnes, making it a promising candidate for use in cosmetic formulations and skin applications. Its effect on S. pneumoniae, combined with its excellent tolerability profile on lung cells, also makes this new product suitable for applications involving the respiratory tract.