Influence of crosslinkerconcentration onthecharacteristics of erythropoietin-alginate microspheres

Abstract

Context: Microspheres have several advantages including protecting proteins from degradation and clearance after administration and produce a long-term therapeutic effect. Erythropoietin as a neuroprotectant agent has protein-like properties, which are susceptible to degradation and have low in vivo bioavailability. Microspheres formulations is one of potential drug delivery system for erythropoietin. Aims: To evaluate the effect of CaCl2 concentration on the characteristics (particle size, morphology, swelling index, and yield) of erythropoietin-alginate microspheres. Methods: Erythropoietin-alginate microspheres prepared by ionotropic gelation method with aerosolization technique using sodium alginate as polymer and CaCl2 as crosslinker were dried using freeze drying method with maltodextrin as lyoprotectant. The concentrations of alginate used were 2%, and CaCl2 concentrations were 0.5 M(F1), 0.75 M(F2) and 1 M(F3). Results: Results showed smooth and spherical microspheres for all formula with average particle size were 3.23 ± 0.05 μm (F1); 2.99 ± 0.07 μm (F2); and 2.86 ± 0.03 μm (F3). Mass swelling index at 24 h were 1.25 ± 0.10 (F1), 1.18 ± 0.11 (F2), and 1.11 ± 0.10 (F3); at 30 h were 2.00 ± 1.25 (F1), 1.85 ± 0.14 (F2), and 1.72 ± 0.15 (F3) while particle size swelling index at 24 h were 1.15 ± 0.10 (F1), 1.11 ± 0.10 (F2), and 0.97 ± 0.10 (F3); at 30 h were 1.81 ± 0.09 (F1), 1.73 ± 0.15 (F2), and 1.54 ± 0.14 (F3). Respectively yield percentages were 77.76 ± 6.49, 80.01 ± 3.53, and 82.97 ± 4.22. By using One Way ANOVA, it was found that there were significantly differences between three formulas. Conclusions: The particle size of formulas decreased by increasing concentration of CaCl2, whereas no significant difference on swelling index and yield from microspheres with increasing CaCl2 concentration simultaneously.