Calcium phosphate microspheres for localised delivery of a therapeutic enzyme

The ability of calcium titanium phosphate (CTP) and hydroxyapatite (HAp) microspheres to reversibly adsorb the enzyme glucocerebrosidase (GCR) while preserving its biological activity, and efficiently deliver it to Gaucher disease (GD) fibroblasts was investigated. CTP microspheres adsorbed ca. 3.6-fold more GCR than HAp microspheres. The activity of adsorbed GCR was higher than the free enzyme in the case of CTP microspheres and lower when HAp was used. GCR release from both types of microspheres was characterized by the initial elution of a large percentage of enzyme followed by a delayed release that extended for at least 30 days. Released GCR was internalized by GD fibroblasts increasing their intracellular enzymatic activity. In cells treated with the same amount of GCR-loaded CTP microspheres or free-GCR a higher intracellular activity was detected in the former case, suggesting an improved efficacy.