| Title | Biological evaluation of calcium alginate microspheres as a vehicle for the localized delivery of a therapeutic enzyme |
| Publication Type | Journal Article |
| 2005 |
| Authors | Barrias, CC, Lamghari, M, Granja, PL, Sá Miranda, MC, Barbosa, MA |
| Journal | Journal of Biomedical Materials Research - Part AJ. Biomed. Mater. Res. Part A |
| Volume | 74 |
| Issue | 4 |
| Pagination | 545 - 552 |
| Date Published | 2005/// |
| 00219304 (ISSN) |
| Alginates, alginic acid, article, Bone, bone disease, Bone Regeneration, Calcium alginate, Calcium Compounds, catalysis, Cell culture, Cells, Cultured, controlled study, Drug Carriers, drug delivery system, enzyme activity, enzyme assay, enzyme replacement, Enzymes, Enzymes, Immobilized, fibroblast culture, Fibroblasts, Gaucher disease, Gaucher disease (GD), Glucocerebrosidase (GCR), Glucosylceramidase, Glucuronic Acid, Hexuronic Acids, human, human cell, Humans, iodine 125, Localized delivery, lysosome enzyme, lysosome storage disease, microsphere, Microspheres, Pathology, pH effects, physiology, recombinant enzyme, Therapeutic enzyme |
| Gaucher disease (GD) is caused by the decreased activity and/or stability of the lysosomal enzyme glucocerebrosidase (GCR). The available treatment consists in the intravenous administration of exogenous GCR, and is effective in reverting most of the symptoms. However, in terms of bone pathology, which is among the most disabling manifestations, a slow and incomplete response is observed, indicating that adjuvant therapies are necessary to consistently restore GCR activity in bone and accelerate regeneration. In this study, calcium alginate microspheres were analyzed as a vehicle for localized GCR delivery to bone. Results demonstrated that the entrapped enzyme retained full activity and exhibited a broader pH-dependent activity profile, compared to that of free-GCR, with improved stability at physiological pH. GCR release profile was established, and it was demonstrated that GCR could be released in a sustained manner. The biological behavior of the system was evaluated by analyzing the uptake of released GCR by GCR-deficient cells from GD patients, using different techniques: GCR activity measurements, radiolabeling, and cellulose acetate electrophoresis. Results demonstrated that GCR was internalized by cells significantly enhancing the residual enzymatic activity. To achieve an activity reconstitution level comparable to that obtained using free-GCR, only half of the dose was required with entrapped-GCR. © 2005 Wiley Periodicals, Inc. |
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