Aim

Synthesis and evaluation of an entirely S-protected chitosan as mucoadhesive excipient for vaginal drug delivery.

Methods

N-acetyl-cysteine was linked to 6-mercaptonicotinamide via disulphide exchange reaction. The obtained ligand, NAC-6-MNA, was subsequently attached to chitosan by carbodiimide mediated amide bond formation in two concentrations. The synthesized S-protected chitosan was chemically characterized and mucoadhesive properties and stability against oxidation were investigated. Moreover, metronidazole tablets comprising the S-protected chitosan were evaluated regarding water uptake capacity, disintegration behaviour, residence time on vaginal mucosa, release of the encapsulated drug and antimicrobial activity.

Results

S-protected chitosan displayed 160 ± 19 (CS-MNA-160) and 320 ± 38 (CS-MNA-320) µmol of ligand per gram of polymer. At pH 4.2, CS-MNA-160 and CS-MNA-320 showed 5.2-fold and 6.2-fold increase in mucus viscosity in comparison to unmodified chitosan (One-way ANOVA, p < .001), whereas, 9.9-fold (CS-MNA-160) and 15.6-fold (CS-MNA-320) (One-way ANOVA, p < .001) increase in viscosity was measured at pH 6. The S-protected chitosan remained stable against oxidation in presence of 0.5% v/v hydrogen peroxide. Metronidazole tablets consisting in S-protected chitosan showed prolonged residence time on vaginal mucosa and improved water uptake capacity and disintegration time in comparison to tablets consisting of unmodified chitosan. Moreover, CS-MNA-320 metronidazole tablets displayed prolonged drug release and antimicrobial activity.

Conclusions

On the basis of the achieved results, entirely S-protected chitosan represents a promising excipient for the development of metronidazole vaginal tablets.

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