title: Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer hydrophobicity on PYY3-36 delivery.
abstract: 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.
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland. juha.monkare@uef.fi
authors.forename: Juha
authors.initials: J
authors.lastname: Mönkäre
authors.forename: Risto A
authors.initials: RA
authors.lastname: Hakala
authors.forename: Miia
authors.initials: M
authors.lastname: Kovalainen
authors.forename: Harri
authors.initials: H
authors.lastname: Korhonen
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.forename: Jukka V
authors.initials: JV
authors.lastname: Seppälä
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
mesh_terms: D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D055103:Hypodermoclysis / Q000379:methods; D008297:Male; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013387:Succinic Anhydrides / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D010446:Peptide Fragments; D011108:Polymers; D011208:Powders; D013387:Succinic Anhydrides; D019894:Peptide YY; C061785:peptide YY (3-36)