Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia.


Journal

International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578

Informations de publication

Date de publication:
15 Aug 2019
Historique:
received: 28 01 2019
revised: 27 05 2019
accepted: 30 05 2019
pubmed: 4 6 2019
medline: 18 12 2019
entrez: 4 6 2019
Statut: ppublish

Résumé

Xerostomia is caused by different factors such as side effects of medication, radiotherapy by head and neck cancer as well as Sjögren syndrome. The goal was to synthesize novel preactivated chitosan conjugates and to design adhesive dosage forms comprising sialagogue pilocarpine. Unmodified chitosan (CH) was covalently linked to sulfhydryl possessing mercaptonicotinic acid (MNA) via amide bond formation. In a second step, preactivation occurred via disulfide bond establishment between sulfhydryl linked chitosan and preactivation ligand MNA. Mucoadhesive and mucoprotective properties were scrutinized on buccal mucosa. Safety assessment was performed on head and neck squamous cells. Histology assay was conducted on buccal tissue. Pilocarpine was scrutinized in terms of controlled release behavior. Novel preactivated CH was successfully synthesized and considered as not harmful to the cells at all. Furthermore, mucoadhesion was 1.3-fold improved in the presence of preactivated chitosan as compared to respective unmodified one. Pilocarpine exhibited a 3.1-fold controlled release in presence of novel synthesized chitosan as in comparison to unmodified CH. The novelty of this promising polymeric carrier lies in the synthesis procedure leading to a pronounced mucoadhesive, mucoprotecting and controlled release encouraging dosage form in the management of xerostomia.

Sections du résumé

BACKGROUND BACKGROUND
Xerostomia is caused by different factors such as side effects of medication, radiotherapy by head and neck cancer as well as Sjögren syndrome.
AIM OBJECTIVE
The goal was to synthesize novel preactivated chitosan conjugates and to design adhesive dosage forms comprising sialagogue pilocarpine.
METHODS METHODS
Unmodified chitosan (CH) was covalently linked to sulfhydryl possessing mercaptonicotinic acid (MNA) via amide bond formation. In a second step, preactivation occurred via disulfide bond establishment between sulfhydryl linked chitosan and preactivation ligand MNA. Mucoadhesive and mucoprotective properties were scrutinized on buccal mucosa. Safety assessment was performed on head and neck squamous cells. Histology assay was conducted on buccal tissue. Pilocarpine was scrutinized in terms of controlled release behavior.
RESULTS RESULTS
Novel preactivated CH was successfully synthesized and considered as not harmful to the cells at all. Furthermore, mucoadhesion was 1.3-fold improved in the presence of preactivated chitosan as compared to respective unmodified one. Pilocarpine exhibited a 3.1-fold controlled release in presence of novel synthesized chitosan as in comparison to unmodified CH.
CONCLUSION CONCLUSIONS
The novelty of this promising polymeric carrier lies in the synthesis procedure leading to a pronounced mucoadhesive, mucoprotecting and controlled release encouraging dosage form in the management of xerostomia.

Identifiants

pubmed: 31158424
pii: S0141-8130(19)30711-1
doi: 10.1016/j.ijbiomac.2019.05.219
pii:
doi:

Substances chimiques

Adhesives 0
Drug Carriers 0
Protective Agents 0
Pilocarpine 01MI4Q9DI3
Chitosan 9012-76-4

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1043-1051

Informations de copyright

Copyright © 2019. Published by Elsevier B.V.

Auteurs

Flavia Laffleur (F)

Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria. Electronic address: Flavia.Laffleur@uibk.ac.at.

Sonja Röttges (S)

Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.

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Classifications MeSH