{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:51:36Z","timestamp":1792759896735,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye\u2019s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween\u00ae 80, Tween\u00ae 20, Solutol\u00ae HS15, and Cremophor\u00ae EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween\u00ae 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol\u00ae PGMC, Tween\u00ae 80, and Transcutol\u00ae P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be \u02c250 nm), size homogeneity (PDI &lt; 0.2), emulsion time (around 40 s), transparency, drug content (&gt;90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010125","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T11:28:46Z","timestamp":1705577326000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Formulating Resveratrol and Melatonin Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Ocular Administration Using Design of Experiments"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-9457","authenticated-orcid":false,"given":"Elide","family":"Zingale","sequence":"first","affiliation":[{"name":"Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3392-1258","authenticated-orcid":false,"given":"Angela","family":"Bonaccorso","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata Grazia","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, Section of Systems Biology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosamaria","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-8265","authenticated-orcid":false,"given":"Velia","family":"D\u2019Agata","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Sciences, University of Catania, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-3980","authenticated-orcid":false,"given":"Jarkko","family":"Rautio","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-4192","authenticated-orcid":false,"given":"Rosario","family":"Pignatello","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Role of Sirtuin 1 in the Pathogenesis of Ocular Disease (Review)","volume":"42","author":"Zhou","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","article-title":"The Sirtuin Family in Health and Disease","volume":"7","author":"Wu","year":"2022","journal-title":"Signal Transduct. Target. 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