title: Glycol chitosan as a stabilizer for protein encapsulated into poly(lactide-co-glycolide) microparticle.
abstract: Glycol chitosan (GC), a chitosan derivative conjugated with ethylene glycol, is soluble in water at a neutral/acidic pH and is viscous. This GC was incorporated into poly(lactide-co-glycolide) (PLGA) microparticles (prepared by the multi-emulsion W(1)/O/W(2) (water-in-oil-in-water) method) to stabilize lysozyme (Lys) used as a model protein. Herein, GC's viscous property helped to improve Lys encapsulation efficacy and reduce Lys denaturaton at the water/organic solvent interface. When the GC concentration in the W(1) phase increased, the formation of non-covalent Lys aggregates decreased. This may be because the aqueous microdroplets surrounded by the firm viscous interface protect Lys from the degrading environment formed by the water/organic solvent interface. In an in vitro Lys release test, 40mg incorporation of GC led to continuous Lys release of up to 78wt.% for 1 month and presented bioactivity of more than 95% for Lys released from microparticles. In addition, there was negligible immune response in the tissue treated with the GC-incorporated PLGA microparticles, whereas there was a moderate foreign body reaction in the muscle layer and many configurations of neutrophils in the tissue treated with the PLGA microparticles without GC. It is expected that GC facilitates a decrease in immune responses exacerbated as a consequence of PLGA degradation.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way Suite 315, Salt Lake City, UT 84108, USA.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.forename: Keun-Hong
authors.initials: KH
authors.lastname: Park
authors.forename: In Suh
authors.initials: IS
authors.lastname: Park
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage*; D005549:Foreign-Body Reaction; D019344:Lactic Acid / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000633:toxicity; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D011108:Polymers; D011506:Proteins; C118638:glycol-chitosan; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D009113:Muramidase