Design of a self-unfolding delivery concept for oral administration of macromolecules

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Design of a self-unfolding delivery concept for oral administration of macromolecules. / Jørgensen, Jacob R.; Thamdrup, Lasse H.E.; Kamguyan, Khorshid; Nielsen, Line H.; Nielsen, Hanne M.; Boisen, Anja; Rades, Thomas; Müllertz, Anette.

In: Journal of Controlled Release, Vol. 329, 2021, p. 948-954.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jørgensen, JR, Thamdrup, LHE, Kamguyan, K, Nielsen, LH, Nielsen, HM, Boisen, A, Rades, T & Müllertz, A 2021, 'Design of a self-unfolding delivery concept for oral administration of macromolecules', Journal of Controlled Release, vol. 329, pp. 948-954. https://doi.org/10.1016/j.jconrel.2020.10.024

APA

Jørgensen, J. R., Thamdrup, L. H. E., Kamguyan, K., Nielsen, L. H., Nielsen, H. M., Boisen, A., Rades, T., & Müllertz, A. (2021). Design of a self-unfolding delivery concept for oral administration of macromolecules. Journal of Controlled Release, 329, 948-954. https://doi.org/10.1016/j.jconrel.2020.10.024

Vancouver

Jørgensen JR, Thamdrup LHE, Kamguyan K, Nielsen LH, Nielsen HM, Boisen A et al. Design of a self-unfolding delivery concept for oral administration of macromolecules. Journal of Controlled Release. 2021;329:948-954. https://doi.org/10.1016/j.jconrel.2020.10.024

Author

Jørgensen, Jacob R. ; Thamdrup, Lasse H.E. ; Kamguyan, Khorshid ; Nielsen, Line H. ; Nielsen, Hanne M. ; Boisen, Anja ; Rades, Thomas ; Müllertz, Anette. / Design of a self-unfolding delivery concept for oral administration of macromolecules. In: Journal of Controlled Release. 2021 ; Vol. 329. pp. 948-954.

Bibtex

@article{976cdabdf1264cd4b0268737281c24ad,
title = "Design of a self-unfolding delivery concept for oral administration of macromolecules",
abstract = "Delivering macromolecular drugs, e.g. peptides, to the systemic circulation by oral administration is challenging due to their degradation in the gastrointestinal tract and low transmucosal permeation. In this study, the concept of an oral delivery device utilizing an elastomeric material is presented with the potential of increasing the absorption of peptides, e.g. insulin. Absorption enhancement in the intestine is proposed as a result of self-unfolding of a polydimethylsiloxane foil upon release from enteric coated capsules. A pH-sensitive polymer coating prevents capsule disintegration until arrival in the small intestine where complete unfolding of the elastomeric foil ensures close contact with the intestinal mucosa. Foils with close-packed hexagonal compartments for optimal drug loading are produced by casting against a deep-etched silicon master. Complete unfolding of the foil upon capsule disintegration is verified in vitro and the insulin release profile of the final delivery device confirms insulin protection at gastric pH. In vivo performance is evaluated with the outcome of quantifiable plasma insulin concentrations in all rats receiving duodenal administration of the novel delivery device. By taking advantage of elastomeric material properties for drug delivery, this approach might serve as inspiration for further development of commercially viable biocompatible devices for oral delivery of macromolecules.",
keywords = "Delivery devices, Elastomers, Oral insulin, Permeation enhancers, Polydimethylsiloxane, Protease inhibitors",
author = "J{\o}rgensen, {Jacob R.} and Thamdrup, {Lasse H.E.} and Khorshid Kamguyan and Nielsen, {Line H.} and Nielsen, {Hanne M.} and Anja Boisen and Thomas Rades and Anette M{\"u}llertz",
year = "2021",
doi = "10.1016/j.jconrel.2020.10.024",
language = "English",
volume = "329",
pages = "948--954",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Design of a self-unfolding delivery concept for oral administration of macromolecules

AU - Jørgensen, Jacob R.

AU - Thamdrup, Lasse H.E.

AU - Kamguyan, Khorshid

AU - Nielsen, Line H.

AU - Nielsen, Hanne M.

AU - Boisen, Anja

AU - Rades, Thomas

AU - Müllertz, Anette

PY - 2021

Y1 - 2021

N2 - Delivering macromolecular drugs, e.g. peptides, to the systemic circulation by oral administration is challenging due to their degradation in the gastrointestinal tract and low transmucosal permeation. In this study, the concept of an oral delivery device utilizing an elastomeric material is presented with the potential of increasing the absorption of peptides, e.g. insulin. Absorption enhancement in the intestine is proposed as a result of self-unfolding of a polydimethylsiloxane foil upon release from enteric coated capsules. A pH-sensitive polymer coating prevents capsule disintegration until arrival in the small intestine where complete unfolding of the elastomeric foil ensures close contact with the intestinal mucosa. Foils with close-packed hexagonal compartments for optimal drug loading are produced by casting against a deep-etched silicon master. Complete unfolding of the foil upon capsule disintegration is verified in vitro and the insulin release profile of the final delivery device confirms insulin protection at gastric pH. In vivo performance is evaluated with the outcome of quantifiable plasma insulin concentrations in all rats receiving duodenal administration of the novel delivery device. By taking advantage of elastomeric material properties for drug delivery, this approach might serve as inspiration for further development of commercially viable biocompatible devices for oral delivery of macromolecules.

AB - Delivering macromolecular drugs, e.g. peptides, to the systemic circulation by oral administration is challenging due to their degradation in the gastrointestinal tract and low transmucosal permeation. In this study, the concept of an oral delivery device utilizing an elastomeric material is presented with the potential of increasing the absorption of peptides, e.g. insulin. Absorption enhancement in the intestine is proposed as a result of self-unfolding of a polydimethylsiloxane foil upon release from enteric coated capsules. A pH-sensitive polymer coating prevents capsule disintegration until arrival in the small intestine where complete unfolding of the elastomeric foil ensures close contact with the intestinal mucosa. Foils with close-packed hexagonal compartments for optimal drug loading are produced by casting against a deep-etched silicon master. Complete unfolding of the foil upon capsule disintegration is verified in vitro and the insulin release profile of the final delivery device confirms insulin protection at gastric pH. In vivo performance is evaluated with the outcome of quantifiable plasma insulin concentrations in all rats receiving duodenal administration of the novel delivery device. By taking advantage of elastomeric material properties for drug delivery, this approach might serve as inspiration for further development of commercially viable biocompatible devices for oral delivery of macromolecules.

KW - Delivery devices

KW - Elastomers

KW - Oral insulin

KW - Permeation enhancers

KW - Polydimethylsiloxane

KW - Protease inhibitors

U2 - 10.1016/j.jconrel.2020.10.024

DO - 10.1016/j.jconrel.2020.10.024

M3 - Journal article

C2 - 33086101

AN - SCOPUS:85093917264

VL - 329

SP - 948

EP - 954

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 257326597