title: Preparation and characterization of a composite PLGA and poly(acryloyl hydroxyethyl starch) microsphere system for protein delivery.
abstract: OBJECTIVE
  To prepare and characterize a novel composite microsphere system based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(acryloyl hydroxyethyl starch) (acHES) hydrogel for controlled protein delivery.
  
  
  METHODS
  Model proteins, bovine serum albumin, and horseradish peroxidase were encapsulated in the acHES hydrogel, and then the protein-containing acHES hydrogel particles were fabricated in the PLGA matrix by a solvent extraction or evaporation method. The protein-loaded PLGA-acHES composite microspheres were characterized for protein loading efficiency, particle size, and in vitro protein release. Protein stability was examined by size-exclusion chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and monitoring the enzymatic activity.
  
  
  RESULTS
  Scanning electron microscopy showed discrete PLGA microspheres containing many acHES particles. The composite microspheres were spherical and smooth in size range of 39-93 microm. The drug loading efficiency ranged from 51 to 101%. The composite microspheres showed more favorable in vitro release than conventional PLGA microspheres. The composite microspheres showed 20% less initial with a gradual sustained release compared to high burst (approximately 60%) followed by a very slow release with the conventional PLGA microspheres. The composite microspheres also stabilized encapsulated proteins from the loss of activity during the microsphere preparation and release. Proteins extracted from the composite microspheres showed good stability without protein degradation products and structural integrity changes in the size-exclusion chromatography and SDS-PAGE analyses. Horseradish peroxidase extracted from microspheres retained more than 81% enzymatic activity.
  
  
  CONCLUSIONS
  The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Woo
authors.forename: G
authors.initials: G
authors.lastname: Jiang
authors.forename: Y W
authors.initials: YW
authors.lastname: Jo
authors.forename: P P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006735:Horseradish Peroxidase / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013213:Starch / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D011108:Polymers; D011506:Proteins; D014753:Vinyl Compounds; C106579:poly(acryloylhydroxyethyl starch); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D013213:Starch; D006735:Horseradish Peroxidase