Oral Delivery of the Vancomycin Derivative FU002 by a Surface-Modified Liposomal Nanocarrier.

Oral delivery of peptide therapeutics faces multiple challenges due to their instability in the gastrointestinal tract and low permeation capability. In this study, we aimed to develop a liposomal nanocarrier formulation to enable the oral delivery of the vancomycin-peptide derivative FU002. FU002 is a promising, resistance-breaking, antibiotic which exhibits poor oral bioavailability limiting its potential therapeutic use. To increase its oral bioavailability, we incorporated FU002 into tetraether lipid-stabilized liposomes modified with cyclic cell-penetrating peptides on the liposomal surface. This liposomal formulation showed strong binding to Caco-2 cells without exerting cytotoxic effects in vitro. Pharmacokinetics studies in vivo in rats revealed increased oral bioavailability of liposomal FU002 when compared to the free drug. In vitro and in vivo antimicrobial activity of FU002 was preserved in the liposomal formulation. As highlight, oral administration of liposomal FU002 resulted 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. This article is protected by copyright. All rights reserved.