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: Jiratchaya Mokkaphan, Wijit Banlunara, Tanapat Palaga, Premsuda Sombuntham, Supason Wanichwecharungruang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 6 Issue 22 Pg. 20188-96 (Nov 26 2014) ISSN: 1944-8252 [Electronic] United States
• PMID: 25314005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Drug Carriers
• Lipopolysaccharides
• Propylamines
• Silanes
• Silicones
• Nitric Oxide
• Budesonide
• Interferon-gamma
• amino-propyl-triethoxysilane

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Budesonide (chemistry, pharmacology)
• Cell Line
• Drug Carriers (chemistry)
• Interferon-gamma (pharmacology)
• Lipopolysaccharides (toxicity)
• Macrophages (cytology, drug effects, metabolism)
• Male
• Mice
• Nanoparticles (chemistry)
• Nitric Oxide (metabolism)
• Propylamines
• Rats
• Rats, Wistar
• Silanes (chemistry)
• Silicones (chemistry)