Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 24, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2019.102132
Keywords
Nanoparticles; Polylactide acid; Cell penetrating peptides; Oral delivery; Peptide drugs; Liraglutide
Funding
- Swiss National Science Foundation (SNF) [174975]
- Foundation grant from the Canadian Institutes of Health Research (CIHR) [FDN 148469]
- Innovationsfond Frontier [ZUK 49/2 5.2.160]
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Until today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs. Crown Copyright (C) 2019 Published by Elsevier Inc. All rights reserved.
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