title: Protein release from water-swellable poly(D,L-lactide-PEG)-b-poly(ϵ-caprolactone) implants.
abstract: In this study, water-swellable multiblock copolymers composed of semi-crystalline poly(ϵ-caprolactone) [PCL] blocks and amorphous blocks consisting of poly(D,L-lactide) (PDLLA) and poly(ethylene glycol) (PEG) [PDLLA-PEG] were synthesized. The block ratio of these [PDLLA-PEG]-b-[PCL] multiblock copolymers was varied and the degradation of implants prepared of these polymers by hot melt extrusion (HME) was compared with implants prepared of [PCL-PEG]-b-[PCL], a copolymer which has been described previously (Stanković et al., 2014). It was shown that the initial degradation rate of the [PDLLA-PEG]-b-[PCL] multiblock copolymers increased with increasing the content of amorphous [PDLLA-PEG] block and that the degradation rate of these multiblock copolymers was faster than that of the [PCL-PEG]-b-[PCL] multiblock copolymers due to rapid degradation of the [PDLLA-PEG] block. Furthermore, the release of the model proteins lysozyme and bovine serum albumin from polymer implants prepared by HME was studied. It was found that the protein release from [PDLLA-PEG]-b-[PCL] copolymers was incomplete, which is not acceptable for any application of these polymers. Besides, [PCL-PEG]-b-[PCL] copolymers showed slow and continuous release. We hypothesize that the incomplete release is explained by an irreversible interaction between the proteins and polymer degradation products or by entrapment of the protein in the hydrophobic and non-swellable polymer matrix that was left after degradation and loss of the hydrophilic [PDLLA-PEG] blocks from the degrading polymer.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands. Electronic address: m.stankovic@rug.nl.
authors.forename: Milica
authors.initials: M
authors.lastname: Stanković
authors.affiliation: InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX, Groningen, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Hiemstra
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: de Waard
authors.affiliation: InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX, Groningen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Zuidema
authors.affiliation: InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX, Groningen, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Steendam
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D003692:Delayed-Action Preparations; D004343:Drug Implants; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D011091:Polyesters; D011506:Proteins; D014867:Water; C016240:polycaprolactone; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C033616:poly(lactide); D009113:Muramidase
keywords: Bovine serum albumin; Hot melt extrusion; Lysozyme; Polymer degradation; Polymer implants; Protein–polymer interaction