title: Effect of the molecular weight of poly(ethylene glycol) used as emulsifier on alpha-chymotrypsin stability upon encapsulation in PLGA microspheres.
abstract: Poly(ethylene glycol) (PEG) was used as emulsifier to prepare alpha-chymotrypsin-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres by a solid-in-oil-in-water (s/o/w) technique. The effect of the molecular weight of PEG on protein stability was assessed by the determination of the amount of insoluble aggregates, the activity loss and the magnitude of structural perturbations. In addition, the effect of the molecular weight of PEG on the encapsulation efficiency, microsphere characteristics and release kinetics was investigated. X-ray photoelectron spectroscopy (XPS) was employed to characterize the surface chemistry of the microspheres. Microspheres were prepared using PEG with molecular weight of 6,000, 8,000, 10,000, 12,000 and 20,000. The results indicate that PEG 20,000 was the most effective emulsifier when producing alpha-chymotrypsin-loaded microspheres with respect to protein stability. The aggregate formation was decreased from 18% to 3%; the protein inactivation and the encapsulation-induced structural perturbations were largely prevented. XPS confirmed that PEG was largely located on the surface of microspheres. The molecular weight of PEG affected the microspheres' characteristics and release kinetics. Microspheres prepared with PEG 20,000 showed improved encapsulation efficiency (80%) and a continuous release (for 50 days) with the lowest amount of initial release. It is demonstrated that the selection of the optimum molecular weight of PEG when used as emulsifier in the preparation of microspheres is a critical factor in the development of sustained-release formulations for the delivery of proteins.
authors.affiliation: Department of Chemistry, University of Puerto Rico, Río Piedras Campus, PO Box 23346, San Juan, Puerto Rico 00931-3346. ingridjanneth@yahoo.com
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Castellanos
authors.forename: Giselle
authors.initials: G
authors.lastname: Flores
authors.forename: Kai
authors.initials: K
authors.lastname: Griebenow
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002918:Chymotrypsin / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008863:Microspheres; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D045703:Emulsifying Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D002918:Chymotrypsin; C117608:alpha-chymotrypsin