Mucosa-penetrating liposomes for esophageal local drug delivery
Local drug delivery to the esophagus is hampered by rapid transit time and poor permeability of the mucosa. If some strategies aimed to improve the residence time have been proposed, non-invasive approaches to increase the drug penetration in the mucosa have not been described so far. Herein, we designed mucosa-penetrating liposomes to favor the penetration and retention of curcumin (CURC) in the esophagus.
A novel mucosa penetrating peptide (MPP), SLENKGP, was selected by Phage Display and conjugated to pegylated liposomes at different PEG and MPP’s surface densities. Pegylation assured a long residence time of liposomes (at least 30 min) in the esophagus in vivo, but it did not favor the penetration of CURC in the mucosa. MPP-decorated liposomes instead delivered a significant higher amount of CURC in the mucosa compared to naked pegylated liposomes. Confocal microscopy studies showed that naked pegylated liposomes remain confined in the superficial layers of the mucosa whereas MPP-decorated liposomes penetrate the whole epithelium.
In vitro, MPP reduced the interaction of PEG with mucin, meanwhile favoring the paracellular penetration of liposomes across epithelial cell multilayers. In conclusion, pegylated liposomes represent a valid approach to target the esophagus and the surface functionalization with MPP enhances their penetration in the mucosa.
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Materials
The Ph.D.-7 Phage Display Peptide Library and Escherichia coli K12 strain ER2738 were obtained from New England Biolabs. 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were kindly provided by Lipoid GmbH. Cholesterol (CHOL), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (DSPE-PEG (2000) amine), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000].
Silvia Franzé, Francesco Rama, Edoardo Scarpa, Martina Bruna Violatto, Kaliroi Peqini, Chiara Grazia Milena Gennari, Giulia Anderluzzi, Rebecca Camastra, Anita Salmaso, Giulia Moscatiello, Sara Pellegrino, Loris Rizzello, Paolo Bigini, Francesco Cilurzo, Mucosa-penetrating liposomes for esophageal local drug delivery, International Journal of Pharmaceutics, Volume 661, 2024, 124413, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124413.
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