Design of a self-unfolding delivery concept for oral administration of macromolecules
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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.
I: Journal of Controlled Release, Bind 329, 2021, s. 948-954.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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