title: Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).
abstract: Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R2=0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Adam
authors.initials: A
authors.lastname: Bohr
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yingya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Necati
authors.initials: N
authors.lastname: Harmankaya
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Water
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Stefania
authors.initials: S
authors.lastname: Baldursdottír
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Almdal
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany. Electronic address: moritz.beck-broichsitter@bayer.com.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology*; D006207:Half-Life; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008970:Molecular Weight; D011095:Polyethylenes / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011095:Polyethylenes; D011108:Polymers; C039212:polyethylene carbonate; D012710:Serum Albumin, Bovine; D002787:Sterol Esterase; D012293:Rifampin
keywords: Controlled drug delivery; Molecular weight; Poly(ethylene carbonate); Protein release; Rifampicin; Surface erosion