Titania coating of mesoporous silica nanoparticles for improved biocompatibility and drug release within blood vessels

Farooq, A, Shukur, A, Astley, C, Tosheva, L, Kelly, P, Whitehead, D and Azzawi, M (2018) Titania coating of mesoporous silica nanoparticles for improved biocompatibility and drug release within blood vessels. Acta Biomaterialia, 76. pp. 208-216. ISSN 1742-7061

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Abstract

Blood vessel disease is a major contributor to cardiovascular morbidity and mortality and is hallmarked by dysfunction of the lining endothelial cells (ECs). These cells play a significant role in vascular homeostasis, through the release of mediators to control vessel diameter, hence tissue perfusion. Mesoporous silica nanoparticles (MSNs) can be used as potential drug delivery platforms for vasodilator drugs. Here, using an ex vivo model of vascular function, we examine the use of titania coating for improved biocompatibility and release dynamics of MSN loaded sodium nitroprusside (SNP). MSNs (95 ± 23 nm diameter; pore size 2.7 nm) were synthesised and fully characterised. They were loaded with SNP and coated with titania (TiO2), using the magnetron sputtering technique. Pre-constricted aortic vessels were exposed to drug loaded MSNs (at 1.96 × 1012 MSN mL−1) and the time course of vessel dilation observed, in real time. Exposure of viable vessels to MSNs lead to their internalization into the cytoplasm of ECs, while TiMSNs were also observed in the elastic lamina and smooth muscle cell layers. We demonstrate that titania coating of MSNs significantly improves their biocompatibility and alters the dynamics of drug release. A slow and more sustained relaxation was evident after uptake of TiMSN-SNP, in comparison to uncoated MSN-SNP (rate of dilation was 0.08% per min over a 2.5 h period). The use of titania coated MSNs for drug delivery to the vasculature may be an attractive strategy for therapeutic clinical intervention in cardiovascular disease.