Preparation and detailed characterization of the thiomer chitosan–cysteine as a suitable mucoadhesive excipient for nasal powders

• The chitosan polymer is successfully thiolated with l -cysteine. • Chitosan-cysteine increases nasal mucoadhesion via the formation of disulfide bonds. • A novel method is developed to determine the residual l -cysteine content. • Cytotoxicity studies indicate safe intranasal application of chitosan-cysteine. The therapeutic application of nasal powders requires the development of novel mucoadhesive excipients. Thiolated polymers exhibit significant potential for this purpose based on their increased mucoadhesion attributable to the formation of disulfide bonds between the polymer and mucus surface. A chitosan–cysteine (chit-cyst) conjugate was synthesized using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N -hydroxysuccinimide in aqueous solution. The synthetic yield and synthesis conditions were optimized, and the efficiency of the reaction was evaluated. Rheological measurements revealed that the polymer derivative exhibited increased mucoadhesive properties in comparison to chitosan powder. To characterize the polymer, a novel purity investigation method was developed and verified to investigate the residual l -cysteine content. The results revealed that l -cysteine was not detectable in the resultant polymer matrix. Based on the cytotoxicity studies, chit-cyst was found to be safe for nasal application. Thereafter, nasal powder formulations were prepared using the polymer and the antiparkinsonian drug levodopa methyl ester hydrochloride by freeze-drying to investigate their nasal applicability. Based on the in vitro studies, these powders might be suitable for reducing the off periods of Parkinson’s disease because of their expected higher in vivo mucoadhesion.