title: Microcosmic mechanism of dication for inhibiting acylation of acidic Peptide.
abstract: OBJECTIVE
  For long-effective peptide formulation based on poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, acylation often leads to peptide instability during its release and reduced drug efficacy. Among the reported solving strategies, adding dication such as Ca(2+) and Mn(2+) in the formulation was the most convenient method for inhibiting basic peptide acylation. However, the strategies for the acidic peptide still remain unexplored, possibly due to the peptide's changeable charge state in acid environment within degraded PLGA microspheres. Moreover, the previous studies mainly focusing on the macroscopical adsorption of peptide to PLGA cannot demonstrate the inhibition mechanism.
  
  
  METHODS
  Acylation inhibition for acidic peptide (exenatide) by dications (Ca(2+), Mn(2+) and Zn(2+)) was studied for the first time, and Quartz Crystal Microbalance with Dissipation (QCM-D) was innovatively employed to analyze microcosmic mechanism of the inhibition.
  
  
  RESULTS
  These dications played different roles in acylation inhibition of acidic peptide. The effects of dications on acylation outside or inside PLGA microspheres indicated that Ca(2+) did not work, Mn(2+) played a weak role, and Zn(2+) possessed the greatest inhibition.
  
  
  CONCLUSIONS
  Zn(2+) was the most effective dication for the acylation inhibition because of the complex formation and its steric-hindrance effect, which was a new function for this dication.
authors.affiliation: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
mesh_terms: D000215:Acylation; D002413:Cations, Divalent / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D000077270:Exenatide; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D010455:Peptides / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D014688:Venoms / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D004337:Drug Carriers; D005079:Excipients; D010455:Peptides; D014688:Venoms; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077270:Exenatide