Thesis (M.Sc.)--Chulalongkorn University, 2012

The objective of this research was to prepare a mucoadhesive thiolated chitosan suitable for delivery of hydrophobic drugs. This can be achieved by modification of chitosan with 5-amino-2-mercaptobenzimidazole (MBI) using methyl acrylate (MA) as a linker agent. The substitution of MA was about 14.38% calculated by 1H NMR. The amounts of thiol groups (MBI) and disulfide bonds coupled on MA-CS determined by Ellman’s method were 11.86 and 6.54 μmol per gram of polymer, respectively. Periodic acid: schiff (PAS) colorimetric method was used to study mucin-conjugated polymer bioadhesive strength in the simulated gastrointestinal fluid (pH 1.2, 4.0 and 6.4). The MA-CS and MBI-MA-CS showed stronger mucoadhesive property 10.28 and 11-fold, respectively than that of unmodified chitosan at pH 1.2. Additionally, the applications of CS and modified CS as hydrophobic drug delivery carriers were investigated using simvastatin (SV) as a model drug. The microspheres of CS and modified CS were fabricated using electrospray ionization technique. The swollen particle sizes of microspheres were in the range of 1-5 µm measured by particle sizer. The SV loaded microspheres exhibited over 80% drug entrapment efficiency. The mucoadhesiveness of SV-MA-CS and SV-MBI-MA-CS microspheres displayed 7- and 7.33-fold at pH 1.2, respectively compared to SV-CS. The obtained microspheres not only reduced the burst effect but also prolonged release of SV as long as 12 h.