Synthesis of carboxmethyl chitosan and its effect on budesonide colon sensitive nano release system

Abstract

In this investigation, colon sensitive nanoparticles were prepared using different agents by ion-gelation method. The carboxymethyl chitosan nanoparticles (CMCH-NPs) were used to deliver budesonide to the colon. The formation of Carboxymethyl chitosan (CMCH) was confirmed by H1NMR, FTIR, and degree of substitution (Ds). CMCH-NPs were evaluated for drug excipient interaction, loading efficiency % (LE), entrapment efficiency % (EE), scanning electron microscopy (SEM), zeta potential, particle size distribution, in-vitro release studies (also with enzymes), cytotoxicity, and stability studies. In-vitro release studies by dialysis bag method without enzymes revealed that N4 and N6 showed less than 10% cumulative drug release (% CDR) in pH1.2. SEM results of N6 showed spherical shaped aggregates and smoother surfaces than N4. Consequently, the presence of pepsin in pH 1.2, diastase in pH 4.5 and pancreatin in pH 7.4 buffers did not have any significant effect on the release kinetics of the N6 CMCH-NPs. On addition of the colonic enzymes in 10th hour, there was a marked increase in the release of budesonide (upto 98.27% ± 1.30%) due to the action of enzymes produced by the colonic microflora which causes the lysis of glycosidic bonds. The evidence for pH sensitivity along with the microbiotic activation of the CMCH-NPs in the colon was thus established. The cell viability (%) in all samples was above 96%, ensuring the biocompatibility of CMCH in the dose range of 0.2–2.4 mg/mL. Stability studies as per ICH Q1A (R2) guidelines were found to be stable.

GRAPHICAL ABSTRACT

Keywords:

• Colon drug delivery systems
• polysaccharides
• inflammatory bowel disease
• drug delivery
• Crohn’s Disease
• intermediate colitis
• inflammatory bowel disease
• inflammatory bowel disease therapy
• ulcerative colitis
• carboxymethyl chitosan

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

The authors are thankful to the Management of PES University, Bengaluru, India for providing all the necessary facilities and support through a scholarship to one of the authors to conduct this research work.