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In the present work, the development of liposomes for therapeutic targeted delivery to inflamed endothelia is described. The idea is to exploit a three-step pretargeting system based on the biotin\u2013avidin high-affinity interaction: the first step involves a previously described biotin derivative bearing a VCAM-1 binding peptide; in the second step, the avidin derivative NeutrAvidinTM, which strongly binds to the biotin moiety, is injected; the final step is the administration of biotinylated liposomes that would bind to NeutravidinTM immobilized onto VCAM-1 overexpressing endothelium. Stealth biotinylated liposomes, prepared via the thin film hydration method followed by extrusion and purification via size exclusion chromatography, have been thoroughly characterized for their chemico-physical and morphological features and loaded with metformin hydrochloride, a potential anti-inflammatory agent. The three-step system, tested in vitro on different cell lines via confocal microscopy, FACS analysis and metformin uptake, has proved its suitability for therapeutic applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020235","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T03:22:31Z","timestamp":1707189751000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Development of Biotinylated Liposomes Encapsulating Metformin for Therapeutic Targeting of Inflammation-Based Diseases"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-1805","authenticated-orcid":false,"given":"Giorgia","family":"Ailuno","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4602-6954","authenticated-orcid":false,"given":"Sara","family":"Baldassari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Balboni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Territorial Pharmacy of Azienda Sociosanitaria Ligure 2, Via Carlo Collodi 13, 17100 Savona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-6199","authenticated-orcid":false,"given":"Guendalina","family":"Zuccari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9218-8933","authenticated-orcid":false,"given":"Katia","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, Via Antonio de Toni 14, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-6896","authenticated-orcid":false,"given":"Federica","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-9905","authenticated-orcid":false,"given":"Giuliana","family":"Drava","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-996X","authenticated-orcid":false,"given":"Tullio","family":"Florio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genova, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Caviglioli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, Inflammation, and Cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct. 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