Abstract
The work presented herein discusses the carboxymethylation of kappa-carrageenan, a natural linear polysaccharide, to afford a pH-dependent swelling property allowing for intestinal-targeted delivery of bioactive macromolecules. The carboxymethylation conditions with respect to the volume and concentration of sodium hydroxide ( V NaOH, C NaOH), weight of monochloroacetic acid ( W MCA), and reaction temperature ( T) were optimized using a response surface method incorporating a multivariate spline interpolation technique (RSM S). Fluorescein isothiocyanate-labeled dextran (FD-4; 4.4 kDa) was used as a hydrophilic macromolecule model. Beads made from encapsulating FD-4 in the carboxymethylated kappa-carrageenan displayed pH-dependent swelling and encapsulation efficiency of 74%. The release of FD-4 was low (23 ± 2%) in simulated gastric fluid (SGF) and high (90 ± 3%) in simulated intestinal fluid in a 2 h dissolution study. An additional lambda-carrageenan coating on the surface of the beads further reduced the FD-4 release in SGF. These carboxymethylated kappa-carrageenan beads may provide an efficient alternative approach for the oral delivery of hydrophilic macromolecules to the intestinal tract.
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