Controlled Release of Octreotide and Assessment of Peptide Acylation from Poly(D,L-lactide-co-hydroxymethyl glycolide) Compared to PLGA Microspheres

• Published in: Pharmaceutical research 2012, Vol.29 (1), p.110-120
• Main Authors: Ghassemi, Amir H., van Steenbergen, Mies J., Barendregt, Arjan, Talsma, Herre, Kok, Robbert J., van Nostrum, Cornelus F., Crommelin, Daan J. A., Hennink, Wim E.
• Format: Article
• Language: English
• Subjects: Acromegaly - drug therapy; Acylation; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - chemistry; Antineoplastic Agents, Hormonal - pharmacokinetics; Biochemistry; Biodegradable materials; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Delayed-Action Preparations - pharmacokinetics; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; General pharmacology; Glycolates - chemistry; Humans; Hydrogen-Ion Concentration; Lactic Acid - chemistry; Medical Law; Medical sciences; Microscopy, Electron, Scanning; Microspheres; Neuroendocrine Tumors - drug therapy; Octreotide - administration & dosage; Octreotide - chemistry; Octreotide - pharmacokinetics; Peptides; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Polyesters - chemistry; Polyglycolic Acid - chemistry; Polylactic acid; Polylactic Acid-Polyglycolic Acid Copolymer; Research Paper; Somatostatin - agonists; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-011-0517-3

ABSTRACT Purpose 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.