Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia

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.