title: Silicone surface with drug nanodepots for medical devices.
abstract: An ideal surface of poly(dimethylsiloxane) (PDMS) medical devices requires sustained drug release to combat various tissue responses and infection. At present, a noncovalent surface coating with drug molecules using binders possesses a detachment problem, while covalently linking drug molecules to the surface provides no releasable drug. Here, a platform that allows the deposition of diverse drugs onto the PDMS surface in an adequate quantity with reliable attachment and a sustained-release character is demonstrated. First, a PDMS surface with carboxyl functionality (PDMS-COOH) is generated by subjecting a PDMS piece to an oxygen plasma treatment to obtain silanol moieties on its surface, then condensing the silanols with (3-aminopropyl)triethoxysilane molecules to generate amino groups, and finally reacting the amino groups with succinic anhydride. The drug-loaded carriers with hydroxyl groups on their surface can then be esterified to PDMS-COOH, resulting in a PDMS surface covalently grafted with drug-filled nanocarriers so that the drugs inside the securely grafted carriers can be released. Demonstrated here is the covalent linking of the surface of a PDMS endotracheal tube with budesonide-loaded ethylcellulose nanoparticles. A secure and high drug accumulation at the surface of the tubes (0.025 mg/cm2) can be achieved without changes in its bulk property such as hardness (Shore-A), and sustained release of budesonide with a high release flux during the first week followed by a reduced release flux over the subsequent 3 weeks can be obtained. In addition, the grafted tube possesses more hydrophilic surface and thus is more tissue-compatible. The grafted PDMS pieces show a reduced in vitro inflammation in cell culture and a lower level of in vivo tissue responses, including a reduced level of inflammation, compared to the unmodified PDMS pieces, when implanted in rats. Although demonstrated with budesonide and a PDMS endotracheal tube, this platform of grafting a PDMS surface with drug-loaded particles can be applied to other drugs and other devices.
authors.affiliation: Program of Petrochemical and Polymer Science, Faculty of Science, ‡Department of Pathology, Faculty of Veterinary Science, §Department of Microbiology, Faculty of Science, ∥Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, ⊥Department of Chemistry, Faculty of Science, and #Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University , Bangkok 10330, Thailand.
authors.forename: Jiratchaya
authors.initials: J
authors.lastname: Mokkaphan
authors.forename: Wijit
authors.initials: W
authors.lastname: Banlunara
authors.forename: Tanapat
authors.initials: T
authors.lastname: Palaga
authors.forename: Premsuda
authors.initials: P
authors.lastname: Sombuntham
authors.forename: Supason
authors.initials: S
authors.lastname: Wanichwecharungruang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D019819:Budesonide / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D011437:Propylamines; D051381:Rats; D017208:Rats, Wistar; D012821:Silanes / Q000737:chemistry; D012828:Silicones / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008070:Lipopolysaccharides; D011437:Propylamines; D012821:Silanes; D012828:Silicones; D009569:Nitric Oxide; D019819:Budesonide; D007371:Interferon-gamma; C477625:amino-propyl-triethoxysilane
keywords: drug release; endotracheal tube; implantation; inflammation; silicone surface; surface functionalization