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In this study, the aim is to develop a liposomal nanocarrier formulation to enable the oral delivery of the vancomycin\u2010peptide derivative FU002. FU002 is a promising, resistance\u2010breaking, antibiotic which exhibits poor oral bioavailability, limiting its potential therapeutic use. To increase its oral bioavailability, FU002 is incorporated into tetraether lipid\u2010stabilized liposomes modified with cyclic cell\u2010penetrating peptides on the liposomal surface. This liposomal formulation shows strong binding to Caco\u20102 cells without exerting cytotoxic effects in vitro. Pharmacokinetics studies in vivo in rats reveal increased oral bioavailability of liposomal FU002 when compared to the free drug. In vitro and in vivo antimicrobial activity of FU002 are preserved in the liposomal formulation. As a highlight, oral administration of liposomal FU002 results in significant therapeutic efficacy in a murine systemic infection model. Thus, the presented nanotechnological approach provides a promising strategy for enabling oral delivery of this highly active vancomycin derivative.<\/jats:p>","DOI":"10.1002\/adhm.202303654","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T17:49:36Z","timestamp":1708624176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Oral Delivery of the Vancomycin Derivative FU002 by a Surface\u2010Modified Liposomal Nanocarrier"],"prefix":"10.1002","volume":"13","author":[{"given":"Julia","family":"Werner","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Umst\u00e4tter","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg 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