Mucoadhesive chitosan- and cellulose derivative-based nanofiber-on-foam-on-film system for non-invasive peptide delivery

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Oromucosal administration is an attractive non-invasive route. However, drug absorption is challenged by salivary flow and the mucosa being a significant permeability barrier. The aim of this study was to design and investigate a multi-layered nanofiber-on-foam-on-film (NFF) drug delivery system with unique properties and based on polysaccharides combined as i) mucoadhesive chitosan-based nanofibers, ii) a peptide loaded hydroxypropyl methylcellulose foam, and iii) a saliva-repelling backing film based on ethylcellulose. NFF displays optimal mechanical properties shown by dynamic mechanical analysis, and biocompatibility demonstrated after exposure to a TR146 cell monolayer. Chitosan-based nanofibers provided the NFF with improved mucoadhesion compared to that of the foam alone. After 1 h, >80 % of the peptide desmopressin was released from the NFF. Ex vivo permeation studies across porcine buccal mucosa indicated that NFF improved the permeation of desmopressin compared to a commercial freeze-dried tablet. The findings demonstrate the potential of the NFF as a biocompatible drug delivery system.

Original languageEnglish
Article number120429
JournalCarbohydrate Polymers
Volume303
ISSN0144-8617
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
MBS, HMN, ISC and JJ thank The Danish Council for Independent Research; Technology and Production (DFF-6111-00333) (MBS) and University of Copenhagen for funding this project. MBS and HMN furthermore thank the Novo Nordisk Foundation (Grand Challenge Program; NNF16OC0021948). HÖ, JR and NG acknowledge Nordic POP NordForsk Program Nordic University Hub (Project #85352, Nordic POP, Patient Oriented Products). Department of Experimental Medicine at University of Copenhagen and Department of Veterinary Clinical Sciences are greatly acknowledged for providing porcine tissue for the mucoadhesion and ex vivo studies. The authors acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. Associate Professor Christian Janfelt is acknowledged for support with LC-MS analysis. Xin Zhou is acknowledged for assistance with the high-resolution SEM images of the cross-sections and the electrospun nanofibers. The authors thank LEO Pharma (Ballerup, Denmark) for availability of the dermatome equipment.

Funding Information:
MBS, HMN, ISC and JJ thank The Danish Council for Independent Research ; Technology and Production ( DFF-6111-00333 ) (MBS) and University of Copenhagen for funding this project. MBS and HMN furthermore thank the Novo Nordisk Foundation (Grand Challenge Program; NNF16OC0021948 ). HÖ, JR and NG acknowledge Nordic POP NordForsk Program Nordic University Hub (Project # 85352 , Nordic POP, Patient Oriented Products). Department of Experimental Medicine at University of Copenhagen and Department of Veterinary Clinical Sciences are greatly acknowledged for providing porcine tissue for the mucoadhesion and ex vivo studies. The authors acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. Associate Professor Christian Janfelt is acknowledged for support with LC-MS analysis. Xin Zhou is acknowledged for assistance with the high-resolution SEM images of the cross-sections and the electrospun nanofibers. The authors thank LEO Pharma (Ballerup, Denmark) for availability of the dermatome equipment.

Publisher Copyright:
© 2022 The Authors

    Research areas

  • Biopharmaceuticals, Chitosan, Hydroxypropyl methylcellulose, Mucoadhesion, Oromucosal drug delivery, Peptide

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