title: Tailored protein release from biodegradable poly(ε-caprolactone-PEG)-b-poly(ε-caprolactone) multiblock-copolymer implants.
abstract: In this study, the in vitro release of proteins from novel, biodegradable phase-separated poly(ε-caprolactone-PEG)-block-poly(ε-caprolactone), [PCL-PEG]-b-[PCL]) multiblock copolymers with different block ratios and with a low melting temperature (49-55°C) was studied. The effect of block ratio and PEG content of the polymers (i.e. 22.5, 37.5 and 52.5 wt%) as well as the effect of protein molecular weight (1.2, 5.8, 14, 29 and 66 kDa being goserelin, insulin, lysozyme, carbonic anhydrase and albumin, respectively) on protein release was investigated. Proteins were spray-dried with inulin as stabilizer to obtain a powder of uniform particle size. Spray-dried inulin-stabilized proteins were incorporated into polymeric implants by hot melt extrusion. All incorporated proteins fully preserved their structural integrity as determined after extraction of these proteins from the polymeric implants. In general, it was found that the release rate of the protein increased with decreasing molecular weight of the protein and with increasing the PEG content of the polymer. Swelling and degradation rate of the copolymer increased with increasing PEG content. Hence, release of proteins of various molecular weights from [PCL-PEG]-b-[PCL] multi-block copolymers can be tailored by varying the PEG content of the polymer.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: m.stankovic@rug.nl.
authors.forename: Milica
authors.initials: M
authors.lastname: Stanković
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Tomar
authors.affiliation: InnoCore Pharmaceuticals, Groningen, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Hiemstra
authors.affiliation: InnoCore Pharmaceuticals, Groningen, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Steendam
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
mesh_terms: D020341:Absorbable Implants; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004343:Drug Implants; D007700:Kinetics; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; D011506:Proteins; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); D011092:Polyethylene Glycols
keywords: Controlled release; Hot melt extrusion; Multiblock copolymers; PEG content; Peptide/protein molecular weight; Polymer implants