title: In situ forming acyl-capped PCLA-PEG-PCLA triblock copolymer based hydrogels.
abstract: Sustained intra-articular drug delivery opens up new opportunities for targeted treatment of osteoarthritis. In this study, we investigated the in vitro and in vivo properties and performance of a newly developed hydrogel based on acyl-capped PCLA-PEG-PCLA specifically designed for intra-articular use. The hydrogel formulation consisted of a blend of polymers either capped with acetyl, or with 2-(2',3',5',-triiodobenzoyl, TIB) moieties. TIB was added to visualize the gel using μCT, enabling longitudinal quantification of its degradation. Blends containing TIB-capped polymer degraded in vitro (37 °C; pH 7.4 buffer) through dissolution over a period of ~20 weeks, and degraded slightly faster (~12 weeks) after subcutaneous injection in rats. This in vivo acceleration was likely due to active (enzymatic) degradation, shown by changes in polymer composition and molecular weight as well as the presence of macrophages. After intra-articular administration in rats, the visualized gel gradually lost signal intensity over the course of 4 weeks. Good cytocompatibility of acetyl-capped polymer based hydrogel was proven in vitro on erythrocytes and chondrocytes. Moreover, intra-articular biocompatibility was demonstrated using μCT-imaging and histology, since both techniques showed no changes in cartilage quality and/or quantity.
authors.affiliation: Department of Orthopaedics, Erasmus Medical Centre, Rotterdam, The Netherlands. m.sandker@erasmusmc.nl
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Sandker
authors.forename: Audrey
authors.initials: A
authors.lastname: Petit
authors.forename: Everaldo M
authors.initials: EM
authors.lastname: Redout
authors.forename: Michiel
authors.initials: M
authors.lastname: Siebelt
authors.forename: Benno
authors.initials: B
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Bruin
authors.forename: Ronald
authors.initials: R
authors.lastname: Meyboom
authors.forename: Tina
authors.initials: T
authors.lastname: Vermonden
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Harrie
authors.initials: H
authors.lastname: Weinans
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002356:Cartilage / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects; D016503:Drug Delivery Systems; D006736:Horses; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011091:Polyesters; C512884:poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol); D011092:Polyethylene Glycols
keywords: Biocompatibility; Drug delivery system; Hydrogel; Intra-articular; PCLA–PEG–PCLA; Radiopaque