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Helodermin-loaded nanoparticles: characterization and transport across an in vitro model of the follicle-associated
Anne des Rieux1, Virginie Fievez, Maryam Momtaz
1Unité de Pharmacie Galénique, Université catholique de Louvain, Brussels, Belgium.
Abstract:
M cells represent a potential portal for oral delivery of peptides and proteins due to their high endocytosis abilities. An in vitro model of human FAE (co-cultures) was used to evaluate the influence of M cells on the transport of free and encapsulated helodermin--a model peptide--across the intestinal epithelium. M cells enhanced transport of intact helodermin (18-fold, Papp=3 x 10(-6) cm s(-1)). As pegylation increased nanoparticle transport by M cells, helodermin was encapsulated in 200 nm nanoparticles containing PEG-b-PLA:PLGA 1:1. Stability of the selected formulation was demonstrated in simulated gastric and intestinal fluids. M cells increased the transport of helodermin encapsulated in these nanoparticles by a factor of 415, as compared to Caco-2 cells. Transport of free and encapsulated helodermin occurred most probably by endocytosis. In conclusion, M cells improved helodermin transport across the intestinal epithelium, confirming their high potential for oral delivery of peptides.
Insights
M cells significantly enhance oral peptide delivery. Encapsulating peptides in nanoparticles further amplifies this transport across the intestinal epithelium, showing great potential for drug delivery.
Area of Science:
- Pharmacology
- Biotechnology
- Cell Biology
Background:
- M cells in the follicle-associated epithelium (FAE) possess high endocytic capacity.
- M cells are a potential pathway for oral peptide and protein delivery.
- Helodermin serves as a model peptide for evaluating intestinal transport.
Purpose of the Study:
- To assess the role of M cells in the intestinal transport of free and nanoparticle-encapsulated helodermin.
- To evaluate the efficacy of M cells for oral peptide delivery systems.
- To investigate the influence of nanoparticle formulation on M cell-mediated transport.
Main Methods:
- Utilized an in vitro model of human FAE using co-cultures.
- Compared the transport of free helodermin and helodermin encapsulated in PEG-b-PLA:PLGA nanoparticles across the intestinal epithelium.
- Assessed nanoparticle stability in simulated gastric and intestinal fluids.
- Quantified transport rates using Papp values and fold-enhancement factors.
Main Results:
- M cells enhanced the transport of intact helodermin by 18-fold (Papp = 3 x 10(-6) cm s(-1)).
- Helodermin encapsulated in 200 nm PEG-b-PLA:PLGA nanoparticles showed enhanced stability.
- M cells increased the transport of encapsulated helodermin by 415-fold compared to Caco-2 cells.
- Endocytosis was identified as the likely mechanism for transport of both free and encapsulated helodermin.
Conclusions:
- M cells significantly improve the intestinal transport of helodermin, both free and nanoparticle-encapsulated.
- The use of M cells represents a promising strategy for oral peptide and protein delivery.
- Nanoparticle encapsulation further augments M cell-mediated peptide transport, enhancing oral delivery potential.
