Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin
SCIE
SCOPUS
- Title
- Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin
- Authors
- Hahn, SK; Kim, JS; Shimobouji, T
- Date Issued
- 2007-03-15
- Publisher
- WILEY-LISS
- Abstract
- An injectable hyaluronic acid (HA) microhydrogel was successfully developed as a novel drug carrier for controlled release formulation of protein drugs. HA hydrogels were prepared by the disulfide bond formation of thiolated HA (HA-SH). EPO was loaded in situ during HA-SH hydrogel preparation using an accelerating agent of sodium tetrathionate. The gelation time was drastically reduced from a day to 30 min when sodium tetrathionate was added for HA-SH hydrogel preparation. In vitro release of EPO in PBS at 37 degrees C showed that EPO was rapidly released for 3 days with an initial burst and then slowly up to 9 days from HA-SH hydrogels. HA-SH microhydrogels were prepared by the reactive spray drying of diluted HA-SH precursor solution. The mean particle size was similar to 2.3 mu m and the water content after spray drying was similar to 14%. Ellman's test showed that sodium tetrathionate contributed not only for rapid crosslinking reaction but also for the reduction of residual free thiol content in HA-SH microhydrogels after spray drying. EPO recovery from HA-SH microhydrogels after degradation with hyaluronidase SD was higher than 95%. The released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo release test of EPO from HA-SH microhydrogels in Sprague Dawley (SD) rats, elevated plasma concentration of EPO higher than 0.1 ng/mL, which is a critical minimal concentration for EPO efficacy, was maintained up to 7 days. There was no adverse effect during and after the in vivo tests. (c) 2006 Wiley Periodicals, Inc.
- Keywords
- controlled release; erythropoietin; hyaluronic acid; sodium tetrathionate; disulfide bond; crosslinking; spray drying; microhydrogel; DRUG-DELIVERY; FUNCTIONALIZED DERIVATIVES; SODIUM HYALURONATE; HYDROGELS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/29440
- DOI
- 10.1002/JBM.A.30997
- ISSN
- 1549-3296
- Article Type
- Article
- Citation
- JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, vol. 80A, no. 4, page. 916 - 924, 2007-03-15
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