Optimization of Emulsification Parameters for Preparing Hydrogel Beads Based on an Enzymatically Cross-Linkable Poly(aspartamide) Derivative

In this study, phenolic hydroxyl-functionalized poly(α,β-[<i>N</i>-(2-hydroxyethyl)-D, L-aspartamide]) (PHEA-HP) was used to prepare hydrogel beads via an emulsion-enzymatic gelation process. The effects of the preparation conditions on the size and size distribution span of the hydrogel beads were investigated. Initially, single-factor experiments were conducted to determine the range of preparation conditions for hydrogel beads. Subsequently, a Box-Behnken design combined with response surface methodology (BBD-RSM) was employed to optimize the emulsification parameters for preparing hydrogel beads, with three numerical independent variables (oil-to-water ratio, homogenization rate, and Span 80 dosage) and two responses (size and size distribution span). The results indicated that the size distribution span fit the quadratic model well and was more sensitive to the three independent variables than size. The optimal preparation conditions were validated to be an oil-to-water ratio of 10.3, a homogenization rate of 2930 rpm, and a Span 80 dosage of 2.0%. At the optimum point, the prepared PHEA-HP hydrogel beads were spherical, with an average size of 14.0 ± 0.2 μm and a size distribution span of 0.185 ± 0.010.