A water-soluble methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride as novel mucoadhesive polymeric nanocomplex platform for sustained-release drug delivery

Abstract

A water-soluble chitosan derivative, methylated N-(4-N,N- dimethylaminocinnamyl) chitosan chloride (MDMCMChC) was investigated as novel mucoadhesive polymeric nanocomplex platform for sustained-release drug delivery in comparison with widely used chitosan derivative, N,N,N-trimethylammonium chitosan chloride (TMChC). Diclofenac sodium (DS) was used as model negatively charged drug in this study. The presence of N-(4-N,N,N- trimethylammoniumylcinnamyl) moieties in MDMCMChC resulted in very small (approximately 90 nm) and uniform in size of nanocomplexes, high drug entrapment and sustained release. Ionic interaction between both positively charged chitosan derivatives and DS was confirmed by FT-IR spectroscopy, however, the salt effect study suggested that electrostatic interaction plays an important role on nanocomplex formation of TMChC than MDMCMCh. The nanocomplex formation between MDMCMChC and DS is expected to be initially driven by electrostatic attraction between these two ionic species and later by hydrophobic interaction between the aromatic moiety of MDMCMChC and the aromatic ring of DS, resulting in enhanced molecular association and stabilized nanocomplexes. Moreover, the mucoadhesive property of DS/MDMCMChC nanocomplexes was comparable to TMChC confirmed by surface plasmon response (SPR) method. The obtained results, therefore, revealed high potential of methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride as novel mucoadhesive polymeric nanocomplex platform for sustained-release drug delivery. © 2010 Elsevier Ltd. All rights reserved.