title: Layered superhydrophobic meshes for controlled drug release.
abstract: Layered superhydrophobic electrospun meshes composed of poly(ε-caprolactone) (PCL) and poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, between two 'shield' layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10days corresponding to media infiltrating the shield layer, followed by steady release over >30days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, United States.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Falde
authors.affiliation: Department of Pharmacology, Boston University, Boston, MA, United States.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Freedman
authors.affiliation: Division of Cardiovascular Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: Victoria L M
authors.initials: VL
authors.lastname: Herrera
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, United States; Department of Pharmacology, Boston University, Boston, MA, United States.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Yohe
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, United States.
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, United States; Department of Chemistry, Boston University, Boston, MA, United States. Electronic address: mgrin@bu.edu.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D000077146:Irinotecan; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011091:Polyesters; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility; D013499:Surface Properties
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; D000077146:Irinotecan; D002166:Camptothecin
keywords: Drug delivery; Electrospinning; Electrospun mesh; Lung cancer; Superhydrophobic