title: Sustained release of transgenic human factor IX: preparation, characterization, and in vivo efficacy.
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.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC. lichien@ndmctsgh.edu.tw
authors.forename: Li-Chien
authors.initials: LC
authors.lastname: Chang
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Yang
authors.forename: Anna Chian New
authors.initials: AC
authors.lastname: Chua
authors.forename: Yi-Juain
authors.initials: YJ
authors.lastname: Lin
authors.forename: Sun-Mou
authors.initials: SM
authors.lastname: Lai
mesh_terms: D000818:Animals; D001760:Bleeding Time; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D004655:Emulsions; D004795:Enzyme Stability; D005164:Factor IX / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010314:Partial Thromboplastin Time; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D012995:Solubility; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005164:Factor IX