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A Comparison of Chitosan, Mesoporous Silica and Poly(lactic-co-glycolic) Acid Nanocarriers for Optimising Intestinal Uptake of Oral Protein Therapeutics
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
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2021 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 110, no 1, p. 217-227Article in journal (Refereed) Published
Abstract [en]

Efficacious oral delivery of therapeutic proteins remains challenging and nanoparticulate approaches are gaining interest for enhancing their permeability. In this study, we explore the ability for three comparably sized nanocarriers, with diverse physicochemical properties [i.e., chitosan (CSNP), mesoporous silica nanoparticles (MSNP) and poly(lactic-co-glycolic) acid (PLGA-NP)], to successfully facilitate epithelial uptake of a model protein, ovalbumin (OVA). We report the effect of nanoparticle surface chemistry and nanostructure on protein release, cell toxicity and the uptake mechanism in a Madin Darby Canine Kidney (MDCK) cell model of the intestinal epithelium. All nanocarriers exhibited bi-phasic OVA release kinetics with sustained and incomplete release after 4 days, and more pronounced release from MSNP than either polymeric nanocarriers. CSNP and MSNP displayed the highest cellular uptake, however CSNP was prone to significant dose-dependent toxicity attributed to the cationic surface charge. Approximately 25% of MSNP uptake was governed by a clathrin-independent endocytic mechanism, while CSNP and PLGA-NP uptake was not controlled via any endocytic mechanisms investigated herein. Furthermore, endosomal localisation was observed for CSNP and MSNP, but not for PLGA-NP. These findings may assist in the optimal choice and engineering of nanocarriers for specific intestinal permeation enhancement for oral protein delivery.

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 110, no 1, p. 217-227
Keywords [en]
Chitosan, Macromolecular drug delivery, MDCK cells, Nanoparticle(s), Oral drug delivery, Permeability, Physicochemical properties, Polyglycolic acid (PLGA), Protein delivery, Silica
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:umu:diva-178693DOI: 10.1016/j.xphs.2020.09.026ISI: 000600571800022PubMedID: 32979363Scopus ID: 2-s2.0-85092227207OAI: oai:DiVA.org:umu-178693DiVA, id: diva2:1517783
Available from: 2021-01-14 Created: 2021-01-14 Last updated: 2023-03-23Bibliographically approved

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Lundmark, Richard

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