Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation

Essi Taipaleenmäki, Gustav Christensen, Edit Brodszkij, Sidsel A. Mouritzen, Noga Gal, Sidsel Madsen, Mette Skou Hedemann, Tine Ahrendt Knudsen, Henrik Max Jensen, Sofie Laage Christiansen, Flemming Vang Sparsø, Brigitte Städler*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Crossing the intestinal mucus layer remains a great hurdle in oral drug delivery. The viscous mucus gel protects the body from pathogens but simultaneously traps many types of delivery vehicles, limiting their therapeutic efficacy. We report the assembly of mucopenetrating PEG-based polymer-lipid hybrid vesicles encapsulated in mucoadhesive alginate carriers aiming to increase their residence time in the intestine. The stability of the formulations was evaluated in simulated gastrointestinal conditions, showing negligible subunit leakage in the gastric fluid but a substantial release in the intestinal fluid. Mucopenetration of the free and encapsulated subunits was first demonstrated in vitro in a microfluidic set-up filled with reconstituted porcine mucus and in a mucus-covered co-culture of Caco-2 cells and HT29-MTX-E12 cells. Finally, the free and encapsulated subunits remained adhered in close proximity to the intestinal epithelium after oral administration to rats while the alginate carriers were washed away. In conclusion, the double-encapsulated system with combined mucoadhesive and mucopenetrating properties is a promising alternative drug carrier for oral delivery.

Original languageEnglish
JournalJournal of Controlled Release
Volume322
Pages (from-to)470-485
Number of pages16
ISSN0168-3659
DOIs
Publication statusPublished - 10 Jun 2020

Keywords

  • Alginate
  • Block copolymer
  • Hybrid vesicles
  • Mucoadhesion
  • Mucopenetration
  • Oral formulation

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