Overcoming the Mucosal Barrier: Tetraether Lipid?Stabilized Liposomal Nanocarriers Decorated with Cell?Penetrating Peptides Enable Oral Delivery of Vancomycin

Despite the high medical need for oral peptide delivery, instability in gastrointestinal tract and low mucosal permeation still impede this preferred route of administration. Herein, a liposomal nanocarrier combining two self-reliant strategies to overcome these delivery barriers is reported. This approach enables design system with synergistic properties: tetraether lipids derived from archaea are incorporated into liposomes provide particles stability required traverse stomach. When surface resulting inert modified cell-penetrating peptides, can be achieved. The designed proven effective by uptake glycopeptide antibiotic vancomycin Ussing chamber studies. Efficacy vivo demonstrated naïve rats, where highly increased bioavailability obtained vancomycin, drug known minimally absorbed. In contrast, administration single modification (tetraether lipids) leads substantially lower bioavailability. Therapeutic efficacy antimicrobial activity Galleria mellonella systemic infection mouse model. absence cytotoxic effects demonstrates that strategy might boost application macromolecular drugs general.