Preparation of dual crosslinked alginate–chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system

Abstract

Alginate–chitosan (ALG–CS) blend gel beads were prepared based on Ca 2+ or dual crosslinking with various proportions of alginate and chitosan. The homogeneous solution of alginate and chitosan was dripped into the solution of calcium chloride; the resultant Ca 2+ single crosslinked beads were dipped in the solution of sodium sulfate sequentially to prepare dual crosslinked beads. The dual crosslinkage effectively promoted the stability of beads under gastrointestinal tract conditions. The sustained release profiles of single and dual crosslinked gel beads loaded bovine serum albumin (BSA), a model protein drug, were investigated in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). In SGF, compared to Ca 2+ single crosslinked beads, from which BSA released fast and the cumulative drug release percentages were about 80% of all formations in 4 h, the BSA total release from dual crosslinked gel beads was no more than 3% in 8 h. In SIF and SCF, Ca 2+ single crosslinked beads were disrupted soon associating with the fast drug release. As to the dual crosslinked beads, the BSA total release from the ALG–CS mass ratio 9:1 (81.24%) was higher than that of 7:3 and 5:5 (less than 60%) in 8 h in SIF; the BSA release from all beads was much faster in SCF than in SIF. The dual crosslinked beads incubated in gastrointestinal tract conditions, the BSA cumulative release of ALG–CS mass ratios 9:1, 7:3 and 5:5 were respectively 2.35, 1.96, 1.76% (in SGF 4 h), 82.86, 78.83, 52.91% (in SIF 3 h) and 97.84, 96.81, 87.26% (in SCF 3 h), which suggested that the dual crosslinked beads have potential small intestine or colon site-specific drug delivery property.