title: Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres?
abstract: OBJECTIVE
  The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres.
  
  
  METHODS
  Microparticles were prepared according to the double emulsion method. PEG 400 was added with NGF in the internal aqueous phase (PEG/PLGA ratio 1/1 and 1.8/1). Its effect was investigated through interfacial tension studies. Protein stability was assessed by ELISA.
  
  
  RESULTS
  A novel application of PEG in protein stabilization during encapsulation was evidenced by adsorption kinetics studies. PEG 400 limited the penetration of NGF in the interfacial film of the primary emulsion. Consequently, it stabilized the NGF by reducing the contact with the organic phase. In addition, it avoided the NGF release profile to level off by limiting the irreversible NGF anchorage in the polymer layers. On the other hand, the amount of active NGF released in the early stages was increased. During microparticle preparation, NaCl could be added in the external aqueous phase to modify the structure of microparticles. This allowed to reduce the initial release rate without affecting the protein stability always encountered in the absence of PEG.
  
  
  CONCLUSIONS
  PEG 400 appeared of major interest to achieve a continuous delivery of NGF over seven weeks from biodegradable microparticles prepared by the double emulsion technique.
authors.affiliation: UPRES EA 2169, Faculté de Pharmacie, Angers, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Péan
authors.forename: F
authors.initials: F
authors.lastname: Boury
authors.forename: M C
authors.initials: MC
authors.lastname: Venier-Julienne
authors.forename: P
authors.initials: P
authors.lastname: Menei
authors.forename: J E
authors.initials: JE
authors.lastname: Proust
authors.forename: J P
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D001673:Biodegradation, Environmental; D002214:Capsules / Q000378:metabolism; D003692:Delayed-Action Preparations; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008863:Microspheres; D020932:Nerve Growth Factor / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D020932:Nerve Growth Factor