Double cross-linked pectin beads stable in physiological environment as potential support for biomedical applications

Calcium-pectin beads are largely used for biomedical applications, however, the main drawback is their rapid disintegration in the presence of chelating and non-chelating ions from body fluids. Therefore, the principal goal of this work is to produce stable pectin beads by successive ionic and covalent cross-linking and to test their stability in simulated physiological conditions. For this purpose, native pectin was first de-esterified (DEP) to result a maximum amount of carboxylic groups, then a fraction of the DEP was oxidized with NaIO 4 (OXP) to introduce aldehyde groups susceptible to covalent cross-linking. Finally, the de-methylated and de-methylated/oxidized pectin were mixed and transformed into beads by double cross-linking: ionic with calcium ions and covalent with adipic acid dihydrazide (ADH). The gelling properties, sphericity and shape as well as the morphology and the stability of the beads in different media were investigated. Finally, beads were tested for their capacity to encapsulate and release drug molecule. Therefore, microcapsules were loaded with FITC-dextran, a standard high molecular weight model drug molecule, with high encapsulation efficiency. A remarkable delay in FITC-dextran release was observed for DEP/OXP beads compared to DEP particles. The transport mechanism of solvent and FITC-dextran in/from the DEP/OXP beads was determined as a Fickian diffusion-driven. The viability tests proved that both simple and double cross-linked microcapsules are cytocompatible for the HEK-293 cells at pectin concentrations up to 5.5 mg/mL.