title: Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation.
abstract: Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 ± 0.42 vs. PPX[AMIO, DEX] 0.25 ± 0.42, P < 0.001). The PPX[AMIO, DEX] group was similar to native PPX (PPX 0.38 ± 0.48 vs. PPX[AMIO, DEX] 0.25 ± 0.42, P=NS). PPX-Oxd group adhesions were indistinguishable from controls (PPX-Oxd 2.83 ± 0.41 vs. control 2.75 ± 0.42, P=NS). NTF was reduced in the PPX[AMIO, DEX] group (0.80 ± 0.10 mm) compared to control (1.78 ± 0.13 mm, P < 0.001). Total duration of atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 ± 6.8 s vs. 187.6 ± 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 ± 1.2 s vs. 103.2 ± 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.
authors.affiliation: Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, USA. erik@sintactmed.com dean.ho@ucla.edu.
authors.forename: Erik
authors.initials: E
authors.lastname: Robinson
authors.affiliation: Division of Pediatric Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. skaushal@smail.umaryland.edu.
authors.forename: Sunjay
authors.initials: S
authors.lastname: Kaushal
authors.affiliation: Department of Material Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Justice
authors.initials: J
authors.lastname: Alaboson
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
authors.forename: Sudhish
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Chemical & Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Amogh
authors.initials: A
authors.lastname: Belagodu
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Watkins
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Walker
authors.affiliation: Division of Cardiology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Webster
authors.affiliation: Division of Cardiac Surgery, the Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. pmccart@nmh.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, USA. erik@sintactmed.com dean.ho@ucla.edu and Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA and Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D011817:Rabbits; D014992:Xylenes / Q000737:chemistry*
chemical_list: D000889:Anti-Arrhythmia Agents; D004337:Drug Carriers; D015850:Interleukin-6; D011108:Polymers; D014992:Xylenes; C011055:parylene; D003907:Dexamethasone; D000638:Amiodarone