title: Potential of surface-eroding poly(ethylene carbonate) for drug delivery to macrophages.
abstract: Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated surface erosion (by cholesterol esterase). Drug release studies performed with polymer films indicated a diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order drug release profile was observed from PEC due to the controlled polymer degradation process. When exposed to polymer degradation products the murine macrophage cell line J774A.1 showed less susceptibility to PEC than to PLGA. However, when seeding the macrophages on PLGA and PEC films no relevant difference in cell proliferation/growth kinetics was observed. Overall, this study emphasizes that PEC is an attractive polymer for controlled drug release and could provide superior performance to PLGA for some drug delivery applications including the treatment of macrophage infections.
authors: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors: Adam
authors: A
authors: Bohr
authors: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors: Jorrit J
authors: JJ
authors: Water
authors: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors: Yingya
authors: Y
authors: Wang
authors: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors: Lærke
authors: L
authors: Arnfast
authors: Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany; Present address: Chemical and Pharmaceutical Development, Bayer Pharma AG, Wuppertal, Germany. Electronic address: moritz.beck-broichsitter@bayer.com.
authors: Moritz
authors: M
authors: Beck-Broichsitter
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D008264:Macrophages / Q000187:drug effects; D011095:Polyethylenes / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry; D012293:Rifampin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011095:Polyethylenes; C039212:polyethylene carbonate; D011098:Polyglactin 910; D012293:Rifampin
keywords: Controlled drug delivery; Macrophages; Poly(ethylene carbonate); Rifampicin; Surface erosion