title: Human pancreatic polypeptide in a phospholipid-based micellar formulation.
abstract: OBJECTIVE
  Pancreatic polypeptide (PP) has important glucoregulatory functions and thereby holds significance in the treatment of diabetes and obesity. However, short plasma half-life and aggregation propensity of PP in aqueous solution, limits its therapeutic application. To address these issues, we prepared and characterized a formulation of PP in sterically stabilized micelles (SSM) that protects and stabilizes PP in its active conformation.
  
  
  METHODS
  PP-SSM was prepared by incubating PP with SSM dispersion in buffer. Peptide-micelle association and freeze-drying efficacy of the formulation was characterized in phosphate buffers with or without sodium chloride using dynamic light scattering, fluorescence spectroscopy and circular dichroism. The degradation kinetics of PP-SSM in presence of proteolytic enzyme was determined using HPLC and bioactivity of the formulation was evaluated by in vitro cAMP inhibition study.
  
  
  RESULTS
  PP self-associated with SSM and this interaction was influenced by presence/absence of sodium chloride in the buffer. The formulation was effectively lyophilized, demonstrating feasibility for its long-term storage. The stability of peptide against proteolytic degradation was significantly improved and PP in SSM retained its bioactivity in vitro.
  
  
  CONCLUSIONS
  Self-association of PP with phospholipid micelles addressed the delivery issues of the peptide. This nanomedicine should be further developed for the treatment of diabetes.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Banerjee
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyuksel
mesh_terms: D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008027:Light; D008823:Micelles; D053758:Nanoparticles; D036103:Nanotechnology; D009447:Neuroblastoma / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011489:Protein Denaturation; D011498:Protein Precursors / Q000737:chemistry*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism; D012542:Scattering, Radiation; D012965:Sodium Chloride / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D004337:Drug Carriers; D007004:Hypoglycemic Agents; D008823:Micelles; C043710:PPY protein, human; D010714:Phosphatidylethanolamines; D011498:Protein Precursors; D017476:Receptors, Neuropeptide Y; D005576:Colforsin; D011092:Polyethylene Glycols; D012965:Sodium Chloride; C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide; D000242:Cyclic AMP