Background and the purpose of the study: Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system.
Methods: Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione (GSH) to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum (HS) by measurement of the hemolytic capacity of the complement system after contact with nanoparticles.
Results: The FT-IR and (1)HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate (MMA) homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process.
Major conclusion: It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan.
Keywords: Complement consumption; Glutathione; Mucosal drug delivery; Nanoparticles; Thiolated chitosan.