Sustained release of transgenic human factor IX: preparation, characterization, and in vivo efficacy |
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Authors: | Chang Li-Chien Yang Chi-Yu Chua Anna Chian New Lin Yi-Juain Lai Sun-Mou |
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Institution: | School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC. lichien@ndmctsgh.edu.tw |
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Abstract: | The current regimen of factor IX (FIX) injection is of an episodic format, which leads to limited efficacy. A sustained release dosage form is beneficial in terms of reducing the injection frequency and improving the therapeutic effectiveness. The aim of this study was to formulate a new microsphere form of a FIX-containing preparation to diminish these shortcomings. Using the water-in-oil-in-water (W/O/W) double emulsion technique, injectable long-acting FIX microspheres were prepared with transgenic recombinant human FIX (rhFIX) and poly(lactic-co-glycolic acid) (PLGA) polymer. The rhFIX microspheres prepared had diameters ranging between 25-350 μm and easily passed through a small-gauge-number needle for subcutaneous injection. In in vitro release testing, the microspheres had a sustained release profile featuring an initial burst and sustained release spanning a 5-day period. In in vivo pharmacodynamic testing, normalization of the bleeding of hemophilic mice was maintained for 5 days with microsphere injection as compared with 2 days with native rhFIX. Taken together, these results indicated that long-acting FIX microspheres were successfully prepared for potential use in hemophilic prophylaxis. |
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