Polymeric Lids for Microcontainers for Oral Protein Delivery

Chiara Mazzoni; Rasmus Due Jacobsen; Jacob Mortensen; Jacob Rune Jørgensen; Lukas Vaut; Jette Jacobsen; Carsten Gundlach; Anette Müllertz; Line Hagner Nielsen; Anja Boisen

doi:10.1002/mabi.201900004

Polymeric Lids for Microcontainers for Oral Protein Delivery

Chiara Mazzoni^*, Rasmus Due Jacobsen, Jacob Mortensen, Jacob Rune Jørgensen, Lukas Vaut, Jette Jacobsen, Carsten Gundlach, Anette Müllertz, Line Hagner Nielsen, Anja Boisen

^*Corresponding author for this work

8 Citations (Scopus)

Abstract

Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized.

Original language	English
Article number	1900004
Journal	Macromolecular Bioscience
Volume	19
Issue number	5
ISSN	1616-5187
DOIs	https://doi.org/10.1002/mabi.201900004
Publication status	Published - May 2019

Keywords

microdevices
mucoadhesion
oral drug delivery
polymeric coating
protein

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10.1002/mabi.201900004

Cite this

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abstract = "Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized.",

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author = "Chiara Mazzoni and Jacobsen, {Rasmus Due} and Jacob Mortensen and J{\o}rgensen, {Jacob Rune} and Lukas Vaut and Jette Jacobsen and Carsten Gundlach and Anette M{\"u}llertz and Nielsen, {Line Hagner} and Anja Boisen",

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AU - Mazzoni, Chiara

AU - Jacobsen, Rasmus Due

AU - Mortensen, Jacob

AU - Jørgensen, Jacob Rune

AU - Vaut, Lukas

AU - Jacobsen, Jette

AU - Gundlach, Carsten

AU - Müllertz, Anette

AU - Nielsen, Line Hagner

AU - Boisen, Anja

PY - 2019/5

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AB - Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized.

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JO - Macromolecular Bioscience

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Polymeric Lids for Microcontainers for Oral Protein Delivery

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Keywords

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