The study of a drug coating applied using a cold atmospheric plasma: everolimus coating properties

Coating medical devices with active pharmaceutical ingredients (APIs) such as everolimus is commonly used for therapeutic purposes such as reducing inflammatory responses and preventing restenosis in cardiovascular stents. Traditional coating methods like dipping and spraying require lengthy drying and curing steps, which may expose the API to heat and poses a risk of degradation. Cold atmospheric plasma (CAP) systems, which operate at low temperatures, offer a promising alternative by reducing thermal damage during deposition. The BioDepTM unit, a custom-built CAP system developed by TheraDep Ltd has been used for depositing various biologics and therapeutics on different substrates. In this study, the BiodepTM system was used to deposit everolimus onto titanium discs. The deposition of everolimus through the BiodepTM unit, with and without plasma and also the addition of butylated hydroxytoluene (BHT) was investigated. Everolimus is an anti-proliferative drug commonly used in drug-eluting stents. The coatings were characterised using a variety of analytical techniques, including water contact angle (WCA) analysis, Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, deep ultraviolet (DUV) mapping, and atomic force microscopy (AFM). A reverse-phase high performance liquid chromatography- ultra violet (HPLC/UV) method was developed to quantify the drug deposition and analyse the stability after deposition. Imaging of the coated samples revealed the presence of everolimus rings attributed to the drying of the drug on the surface but no significant morphological changes. WCA analysis indicated a change in surface tension, indicating deposition of everolimus. Raman and FTIR spectroscopy confirmed the presence of everolimus, with lower peak intensities suggesting a low concentration was deposited. The addition of BHT during wet deposition introduced a new FTIR peak, which was absent from the plasma deposited samples, potentially due to BHT oxidation. DUV mapping demonstrated non-uniform coverage of everolimus, while AFM revealed no significant differences in surface roughness between plasma and wet deposition methods. The HPLC/UV method showed no degradation of everolimus after deposition, however drug recovery was variable ranging from 36.9- 67.1 µg/ disc. This study successfully demonstrated the use of CAP to deposit everolimus onto titanium discs, with no degradation of everolimus observed. Although the deposition was effective, further optimisation of the coating and elution processes is necessary to achieve more consistent drug loading and recovery. The findings suggest that the use of the CAP system for deposition holds promise for application in drug-eluting stent coatings.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2025

Author dc:creator

• Frewen, Chloe

Advisors dc:contributor.advisor

• Crean, Abina
• Ryan, Katie

• Cold atmospheric plamce
• Biodep unit
• Everolimus
• Deposition
• HPLC
• RAMAN spectroscopy
• Degradation

Statement dc:rights

• © 2025, Chloe Frewen.

Licence dc:rights.uri

• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/17940

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/17940