title: Low temperature extruded implants based on novel hydrophilic multiblock copolymer for long-term protein delivery.
abstract: Parenteral protein delivery requires preservation of the integrity of proteins and control over the release kinetics. In order to preserve the integrity, parenteral protein delivery formulations typically need to be processed at low temperatures. Therefore, we synthesized a novel low melting biodegradable hydrophilic multiblock copolymer composed of poly (ethylene glycol) and poly (ε-caprolactone) to allow extrusion at relatively low temperatures. We investigated the extrusion characteristics of this polymer and explored a strategy how to control the release of the model protein lysozyme from small diameter extruded implants. It was found that the polymer could be well extruded at temperatures as low as 55 °C. Moreover, lysozyme remained active both during extrusion as well as during release. Lysozyme release kinetics could be tailored by the co-incorporation of an oligosaccharide, inulin, which functions as a pore-forming excipient. It was concluded that this hydrophilic multiblock copolymer has promising characteristics for the preparation by melt extrusion of protein delivery implants with a release profile that is sustained over a period of more than 7 months.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. m.stankovic@rug.nl
authors.forename: Milica
authors.initials: M
authors.lastname: Stanković
authors.forename: Hans
authors.initials: H
authors.lastname: de Waard
authors.forename: Rob
authors.initials: R
authors.lastname: Steendam
authors.forename: Christine
authors.initials: C
authors.lastname: Hiemstra
authors.forename: Johan
authors.initials: J
authors.lastname: Zuidema
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
mesh_terms: D016503:Drug Delivery Systems; D004343:Drug Implants; D057927:Hydrophobic and Hydrophilic Interactions; D007444:Inulin / Q000737:chemistry; D008837:Micrococcus / Q000187:drug effects; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins; D013696:Temperature
chemical_list: D004343:Drug Implants; D011091:Polyesters; D011506:Proteins; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); C016240:polycaprolactone; D011092:Polyethylene Glycols; D007444:Inulin; D009113:Muramidase
keywords: Hot melt extrusion; Implants; Lysozyme; Polymers; Sustained release