Abstract: Nanoparticles have received much attention in the development of transmucosal administration because of the special nano-effectivity. On the basis of the formation of disulphide bonds between thiol groups on polymer and cysteine-rich domains of mucus glycoproteins, the thiolated nanoparticles as carriers can prolong the residence time of drugs on the nasal mucosa and allow a sustained drug release at a given target site. In this study, a novel nanoparticle containing N-acetyl-L-cysteine-g-chitosan conjugate(CS-NAC) was prepared and characterized. Mucoadhesive and swelling properties of CS-NAC conjugates were evaluated in vitro. Release studies were performed with insulin as the model drug. The resulting insulin-loaded CS-NAC nanopartilces had a diameter of 140—210 nm, positive zeta potential values(19.5—31.7 mV) and insulin loading(13%—42%). The physicochemical properties of nanoparticles were affected by the amount of thiol groups. The thiolated chitosan nanoparticles exhibited much higher and faster mucoadhesion than unmodified chitosan nanoparticles. In vitro release studies demonstrate that the insulin-loaded CS-NAC nanopartilces was pH-sensitive delivery systems. At pH=6.8, 58.6% of insulin was released from CS-NAC4 nanoparticles within 15 min, while less than 40% of insulin was release with 24 h at pH=5.4. Therefore, the novel thiolated chitosan nanoparticle appears to be a very promising vehicle for transmucosal insulin drug delivery.

Key words: Chitosan, N-Acetyl-L-cysteine, Nanoparticle, Mucoadhesiveness, Drug release