Gelatin Type A (GA) and sodium alginate (SA) complexes were explored to encapsulate epidermal growth factor (EGF), and thereby to circumvent its proteolytic degradation upon topical application to chronic wounds. Phase diagrams were constructed based on turbidity as a function of GA to SA ratio and pH. Various GA-SA mixtures were compared for polydispersity index, zeta potential, Z-average, and ATR-FTIR spectra. Trypsin digestion and human dermal fibroblast scratch wound assay were done to evaluate the effects of EGF encapsulation. The onset pH values for coacervation and precipitation were closer together in high molecular weight GA (HWGA)-SA reaction mixtures than in low molecular weight GA (LWGA)-SA, which was attributed to strong H-bonding interactions between HWGA and SA probed by ATR-FTIR. EGF incorporation in both HWGA-SA precipitates and LWGA-SA coacervates below the isoelectric point of EGF, but not above it, suggests the contribution of electrostatic interactions between EGF and SA. EGF encapsulated in LWGA-SA coacervates was effectively protected from trypsin digestion and showed better in vitro scratch wound activity compared to free EGF. LWGA-SA coacervates are suggested as a novel delivery system for topical application of EGF to chronic wounds.
Keywords: H-bonding interactions; alginate; coacervate; diabetic foot ulcer; electrostatic interactions; epidermal growth factor (EGF); gelatin; polyelectrolyte complex.