Selectively crosslinked hyaluronic acid hydrogels for sustained release formulation of erythropoietin
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SCOPUS
- Title
- Selectively crosslinked hyaluronic acid hydrogels for sustained release formulation of erythropoietin
- Authors
- Motokawa, K; Hahn, SK; Nakamura, T; Miyamoto, H; Shimoboji, T
- Date Issued
- 2006-09-01
- Publisher
- WILEY-LISS
- Abstract
- A novel sustained release formulation of erythropoietin (EPO) was developed using hyaluronic acid (HA) hydrogels. For the preparation of HA hydrogels, adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and analyzed with H-1 NMR. The degree of HA-ADH modification was about 69%. EPO was in situ encapsulated into HA-ADH hydrogels through a selective cross-linking reaction of bis(sulfosuccinimidyl) suberate (BS3) to hydrazide group (pK(a) = 3.0) of HA-ADH rather than to amine group (pK(a) > 9) of EPO. The denaturation of EPO during HA-ADH hydrogel synthesis was drastically reduced with decreasing pH from 7.4 to 4.8. The specific reactivity of BS3 to hydrazide at pH = 4.8 might be due to its low pKa compared with that of amine. In vitro release of EPO in phosphate buffered saline at 37 degrees C showed that EPO was released rapidly for 2 days and then slowly up to 4 days from HA-ADH hydrogels. When the hydrogels were dried at 37 degrees C for a day, however, longer release of EPO up to 3 weeks could be demonstrated. According to in vivo release test of EPO from HA-ADH hydrogels in SD rats, elevated EPO concentration higher than 0.1 ng/mL could be maintained from 7 days up to 18 days depending on the preparation methods of HAADH hydrogels. There was no adverse effect during and after HA-ADH hydrogel implantation. (c) 2006 Wiley Periodicals, Inc.
- Keywords
- sustained release; erythropoietin; hyaluronic acid; crosslinking; hydrogel; DRUG-DELIVERY; FUNCTIONALIZED DERIVATIVES; CHEMICAL-MODIFICATION; SODIUM HYALURONATE; BIOMATERIALS; PROTEINS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/29570
- DOI
- 10.1002/JBM.A.30757
- ISSN
- 1549-3296
- Article Type
- Article
- Citation
- JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, vol. 78A, no. 3, page. 459 - 465, 2006-09-01
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