title: Nanoparticles based on a hydrophilic polyester with a sheddable PEG coating for protein delivery.
abstract: OBJECTIVE
  To investigate the effect of polyethylene glycol (PEG) in nanoparticles based on blends of hydroxylated aliphatic polyester, poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and PEG-PLGHMGA block copolymers on their degradation and release behavior.
  
  
  METHODS
  Protein-loaded nanoparticles were prepared with blends of varying ratios of PEG-PLGHMGA (molecular weight of PEG 2,000 and 5,000 Da) and PLGHMGA, by a double emulsion method with or without using poly(vinyl alcohol) (PVA) as surfactant. Bovine serum albumin and lysozyme were used as model proteins.
  
  
  RESULTS
  PEGylated particles prepared without PVA had a zeta potential ranging from ~ -3 to ~-35 mV and size ranging from ~200 to ~600 nm that were significantly dependent on the content and type of PEG-block copolymer. The encapsulation efficiency of the two proteins however was very low (<30%) and the particles rapidly released their content in a few days. In contrast, all formulations prepared with PVA showed almost similar particle properties (size: ~250 nm, zeta potential: ~-1 mV), while loading efficiency for both model proteins was rather high (80-90%). Unexpectedly, independent of the type of formulation, the nanoparticles had nearly the same release and degradation characteristics. NMR analysis showed almost a complete removal of PEG in 5 days which explains these marginal differences.
  
  
  CONCLUSIONS
  Protein release and particle degradation are not substantially influenced by the content of PEG, likely because of the fast shedding of the PEG blocks. These PEG shedding particles are interesting system for intracellular delivery of drugs.
authors.affiliation: Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG, Utrecht, The Netherlands.
authors.forename: Neda
authors.initials: N
authors.lastname: Samadi
authors.forename: Mies J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: Joep B
authors.initials: JB
authors.lastname: van den Dikkenberg
authors.forename: Tina
authors.initials: T
authors.lastname: Vermonden
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Maryam
authors.initials: M
authors.lastname: Amidi
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000008:administration & dosage*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage*; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C000598657:poly(lactic-co-glycolic-co-hydroxymethylglycolic acid); C000598658:polyethylene glycol-block-poly(lactic-co-glycolic-co-hydroxymethylglycolic acid); D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D009113:Muramidase