Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

摘要

The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.