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

doi:10.1016/j.jconrel.2020.03.047

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 newspaper › Journal article › Research › peer-review

29 Citations (Scopus)

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 language	English
Journal	Journal of Controlled Release
Volume	322
Pages (from-to)	470-485
Number of pages	16
ISSN	0168-3659
DOIs	https://doi.org/10.1016/j.jconrel.2020.03.047
Publication status	Published - 10 Jun 2020

Keywords

Alginate
Block copolymer
Hybrid vesicles
Mucoadhesion
Mucopenetration
Oral formulation

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10.1016/j.jconrel.2020.03.047

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Taipaleenmäki, E., Christensen, G., Brodszkij, E., Mouritzen, S. A., Gal, N., Madsen, S., Hedemann, M. S., Knudsen, T. A., Jensen, H. M., Christiansen, S. L., Sparsø, F. V., & Städler, B. (2020). Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation. Journal of Controlled Release, 322, 470-485. https://doi.org/10.1016/j.jconrel.2020.03.047

@article{d28956669a0044d4a8e89ec4e5c32e7b,

title = "Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation",

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.",

keywords = "Alginate, Block copolymer, Hybrid vesicles, Mucoadhesion, Mucopenetration, Oral formulation",

author = "Essi Taipaleenm{\"a}ki and Gustav Christensen and Edit Brodszkij and Mouritzen, {Sidsel A.} and Noga Gal and Sidsel Madsen and Hedemann, {Mette Skou} and Knudsen, {Tine Ahrendt} and Jensen, {Henrik Max} and Christiansen, {Sofie Laage} and Spars{\o}, {Flemming Vang} and Brigitte St{\"a}dler",

year = "2020",

month = jun,

day = "10",

doi = "10.1016/j.jconrel.2020.03.047",

language = "English",

volume = "322",

pages = "470--485",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier B.V.",

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Taipaleenmäki, E, Christensen, G, Brodszkij, E, Mouritzen, SA, Gal, N, Madsen, S, Hedemann, MS, Knudsen, TA, Jensen, HM, Christiansen, SL, Sparsø, FV & Städler, B 2020, 'Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation', Journal of Controlled Release, vol. 322, pp. 470-485. https://doi.org/10.1016/j.jconrel.2020.03.047

Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation. / Taipaleenmäki, Essi; Christensen, Gustav; Brodszkij, Edit et al.
In: Journal of Controlled Release, Vol. 322, 10.06.2020, p. 470-485.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Mucopenetrating polymer – Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation

AU - Taipaleenmäki, Essi

AU - Christensen, Gustav

AU - Brodszkij, Edit

AU - Mouritzen, Sidsel A.

AU - Gal, Noga

AU - Madsen, Sidsel

AU - Hedemann, Mette Skou

AU - Knudsen, Tine Ahrendt

AU - Jensen, Henrik Max

AU - Christiansen, Sofie Laage

AU - Sparsø, Flemming Vang

AU - Städler, Brigitte

PY - 2020/6/10

Y1 - 2020/6/10

N2 - 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.

AB - 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.

KW - Alginate

KW - Block copolymer

KW - Hybrid vesicles

KW - Mucoadhesion

KW - Mucopenetration

KW - Oral formulation

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U2 - 10.1016/j.jconrel.2020.03.047

DO - 10.1016/j.jconrel.2020.03.047

M3 - Journal article

C2 - 32243977

AN - SCOPUS:85082779412

SN - 0168-3659

VL - 322

SP - 470

EP - 485

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

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

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Keywords

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