Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin
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Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin. / Stie, Mai Bay; Gätke, Johan Ring; Chronakis, Ioannis S.; Jacobsen, Jette; Nielsen, Hanne Mørck.
In: International Journal of Molecular Sciences, Vol. 23, No. 3, 1458, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin
AU - Stie, Mai Bay
AU - Gätke, Johan Ring
AU - Chronakis, Ioannis S.
AU - Jacobsen, Jette
AU - Nielsen, Hanne Mørck
N1 - Funding Information: Funding: This research was funded by The Danish Council for Independent Research, Technology and Production, grant number DFF-6111-00333; the Novo Nordisk Foundation Grand Challenge Program, NNF16OC0021948; and Innovation Fund Denmark PROBIO, project-7076-00053B. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-in-testinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded muco-adhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmo-pressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber– film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
AB - The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-in-testinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded muco-adhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmo-pressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber– film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
KW - Biopharmaceuticals
KW - Electrospinning
KW - Ex vivo flow retention model
KW - Muco-adhesion
KW - Peptide drug delivery
KW - Sublingual delivery
U2 - 10.3390/ijms23031458
DO - 10.3390/ijms23031458
M3 - Journal article
C2 - 35163377
AN - SCOPUS:85123375131
VL - 23
JO - International Journal of Molecular Sciences (CD-ROM)
JF - International Journal of Molecular Sciences (CD-ROM)
SN - 1424-6783
IS - 3
M1 - 1458
ER -
ID: 291672104