Mucoadhesive Stearate-Gallate-N-Trimethylchitosan micelles for simvastatin delivery carriers

Abstract

This study aimed to prepare a mucoadhesive stearate-gallate-n-trimethylchitosan micelles for simvastatin delivery carriers. This can be achieved by modification of chitosan with gallic acid (GA) and stearic acid (SA) conjugated with N-trimethylchitosan using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAc) as a coupling agent. The results indicated that the degree of quaternization (DQ) of TMC was 24.33%. The substitution of GA and SA was about 5.00 and 21.77 % by ¹H NMR, respectively. Critical micelle concentration (CMC) was found that the SA-GA-TMC was 3.98 µg/mL. Periodic acid: Schiff (PAS) colorimetric method was used to study mucin conjugated polymer in the simulated gastrointestinal fluid (pH 1.2, 4.0 and 6.4). The SA-GA-TMC showed stronger mucoadhesive property 11.15, 5.82 and 7.85 times, respectively than that of unmodified chitosan at pH 1.2, 4.0 and 6.4, respectively. Additionally, the application of SA-GA-TMC as low water soluble drug delivery carriers was investigated using simvastatin (SV) as a model drug. The SV loaded micelles exhibited over 80% drug entrapment efficiency. The mucoadhesiveness of SV-SA-GA-TMC micelles displayed 1.35, 1.51 and 1.68 mg/mL at pH 1.2, 4.0 and 6.4, respectively. The release profiles of SV-SA-GA-TMC showed prolonged and sustained drug release over 24h.