Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin

✍ Scribed by Sei Kwang Hahn; Ji Seok Kim; Tsuyoshi Shimobouji

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 346 KB
• Volume: 80A
• Category: Article
• ISSN: 1549-3296
• DOI: 10.1002/jbm.a.30997

✦ Synopsis

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°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 ∼2.3 μm and the water content after spray drying was ∼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. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006