title: Controlled release of octreotide and assessment of peptide acylation from poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.
abstract: OBJECTIVE
  To investigate the in vitro release of octreotide acetate, a somatostatin agonist, from microspheres based on a hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA).
  
  
  METHODS
  Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 μm) and loading efficiency of 60-70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR(®)); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored.
  
  
  RESULTS
  PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20-60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70-90%); > 60% of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days; > 75% of released peptides were acylated adducts.
  
  
  CONCLUSIONS
  PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres.
authors: Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors: Amir H
authors: AH
authors: Ghassemi
authors: Mies J
authors: MJ
authors: van Steenbergen
authors: Arjan
authors: A
authors: Barendregt
authors: Herre
authors: H
authors: Talsma
authors: Robbert J
authors: RJ
authors: Kok
authors: Cornelus F
authors: CF
authors: van Nostrum
authors: Daan J A
authors: DJ
authors: Crommelin
authors: Wim E
authors: WE
authors: Hennink
mesh_terms: D000172:Acromegaly / Q000188:drug therapy; D000215:Acylation; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D018358:Neuroendocrine Tumors / Q000188:drug therapy; D015282:Octreotide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013004:Somatostatin / Q000819:agonists*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006016:Glycolates; D011091:Polyesters; C544675:poly(lactic-co-hydroxymethyl glycolic acid); C576815:poly(lactide-co-hydroxymethyl glycolide); C031149:glycolic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013004:Somatostatin; D015282:Octreotide