Design, Synthesis, Characterization, and In Vitro Evaluation of a New Cross-Linked Hyaluronic Acid for Pharmaceutical and Cosmetic Applications
Sabrina Sciabica,
Giovanni Tafuro,
Alessandra Semenzato,
Daniela Traini,
Dina M. Silva,
Larissa Gomes Dos Reis,
Luisa Canilli,
Massimo Terno,
Elisa Durini,
Silvia Vertuani,
Anna Baldisserotto,
Stefano Manfredini
Affiliations
Sabrina Sciabica
Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Giovanni Tafuro
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy
Alessandra Semenzato
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy
Daniela Traini
Macquarie Medical School, Department of Medical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University & Woolcock Institute of Medical Research, Sydney 2037, Australia
Dina M. Silva
Macquarie Medical School, Department of Medical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University & Woolcock Institute of Medical Research, Sydney 2037, Australia
Larissa Gomes Dos Reis
Macquarie Medical School, Department of Medical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University & Woolcock Institute of Medical Research, Sydney 2037, Australia
Luisa Canilli
Istituto Ganassini S.p.A., Via Carlo Boncompagni, 63, 20139 Milano, Italy
Massimo Terno
Istituto Ganassini S.p.A., Via Carlo Boncompagni, 63, 20139 Milano, Italy
Elisa Durini
Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Silvia Vertuani
Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Anna Baldisserotto
Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Stefano Manfredini
Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Hyaluronic acid (HA), an excellent biomaterial with unique bio properties, is currently one of the most interesting polymers for many biomedical and cosmetic applications. However, several of its potential benefits are limited as it is rapidly degraded by hyaluronidase enzymes. To improve the half-life and consequently increase performance, native HA has been modified through cross-linking reactions with a natural and biocompatible amino acid, Ornithine, to overcome the potential toxicity commonly associated with traditional linkers. 2-chloro-dimethoxy-1,3,5-triazine/4-methylmorpholine (CDMT/NMM) was used as an activating agent. The new product (HA–Orn) was extensively characterized to confirm the chemical modification, and rheological analysis showed a gel-like profile. In vitro degradation experiments showed an improved resistance profile against enzymatic digestions. Furthermore, in vitro cytotoxicity studies were performed on lung cell lines (Calu-3 and H441), which showed no cytotoxicity.
