Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer hydrophobicity on PYY3-36 delivery

• Published in: European journal of pharmaceutics and biopharmaceutics 2012, Vol.80 (1), p.33-38
• Main Authors: Mönkäre, Juha, Hakala, Risto A., Kovalainen, Miia, Korhonen, Harri, Herzig, Karl-Heinz, Seppälä, Jukka V., Järvinen, Kristiina
• Format: Article
• Language: English
• Subjects: Animals; Bioavailability; Biological and medical sciences; Biological Availability; Controlled release; Delayed-Action Preparations; Drug Delivery Systems - methods; General pharmacology; Humans; Hydrophobic and Hydrophilic Interactions; Hypodermoclysis - methods; Male; Medical sciences; Peptide Fragments; Peptide YY - administration & dosage; Peptide YY - chemistry; Peptide YY - pharmacokinetics; Peptide YY3-36; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Photocrosslinking; Poly(ester anhydride); Polymers - administration & dosage; Polymers - chemistry; Powders - administration & dosage; Powders - chemistry; Powders - pharmacokinetics; Rats; Rats, Wistar; Succinic Anhydrides - chemistry
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.09.011

Functionalization of poly(ester anhydride) oligomers with 12-carbon alkenyl chain delays PYY3-36 release in vivo in comparison with SAH-functionalized oligomers without alkenyl chain. The treatment for many diseases can be improved by developing more efficient peptide delivery technologies, for example, biodegradable polymers. In this work, photocrosslinked poly(ester anhydride)s based on functionalized poly(ε-caprolactone) oligomers were investigated for their abilities to achieve controlled peptide delivery. The effect of oligomer hydrophobicity on erosion and peptide release from poly(ester anhydride)s was evaluated by developing a sustained subcutaneous delivery system for an antiobesity drug candidate, peptide YY3-36 (PYY3-36). Oligomer hydrophobicity was modified with alkenylsuccinic anhydrides containing a 12-carbon alkenyl chain. PYY3-36 was mixed as a solid powder with methacrylated poly(ester anhydride) precursors, and this mixture was photocrosslinked at room temperature to form an implant for subcutaneous administration in rats. The oligomer hydrophobicity controlled the polymer erosion and PYY3-36 release as the increased hydrophobicity via the alkenyl chain prolonged polymer erosion in vitro and sustained in vivo release of PYY3-36. In addition, photocrosslinked poly(ester anhydride)s increased the bioavailability of PYY3-36 by up to 20-fold in comparison with subcutaneous administration of solution, evidence of remarkably improved delivery. In conclusion, this work demonstrates the suitability of photocrosslinked poly(ester anhydride)s for use in peptide delivery.