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1.
Ann Biomed Eng ; 48(1): 271-281, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31441008

ABSTRACT

Drug-eluting stents are now routinely used in the treatment of acute coronary syndromes caused by coronary artery disease. Whilst the sustained release of anti-proliferative drugs from these devices has greatly reduced the need for repeat revascularisation procedures, this approach is not suitable for all patients and appears to delay regrowth of the endothelium, necessitating the use of prolonged dual anti-platelet therapy. Although the development of more advanced stent platforms and drug coatings has produced modest improvements in performance, these devices have not fully addressed the limitations experienced with their first-generation counterparts. In the present study, we developed a novel stent coating that provides controlled sirolimus release from a bioactive polymer (accelerate™ AT) that has previously been shown to support endothelial cell growth in vitro. A bespoke electrospray deposition process provided control over the coating thickness, surface roughness, drug load, and release kinetics. The resultant optimised coating combines rapid release of an anti-proliferative agent from a bioactive polymer coating that promotes re-endothelialisation, thereby offering potential protection against in-stent restenosis and thrombosis. This novel, dual-action coating therefore has significant therapeutic potential, with the enhanced control of drug load and release kinetics offered by electrospray deposition also opening up opportunities for more personalised treatment approaches. Further development and evaluation of these technologies in vitro and in vivo is therefore warranted.


Subject(s)
Drug-Eluting Stents , Polymers/administration & dosage , Sirolimus/administration & dosage , Animals , Cell Survival , Cells, Cultured , Drug Delivery Systems , Drug Liberation , Endothelial Cells/drug effects , Polymers/chemistry , Sirolimus/chemistry , Swine , Technology, Pharmaceutical
2.
Bioresour Technol ; 198: 488-96, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26432053

ABSTRACT

The enzymatic hydrolysis of cellulosic biomass is a key step in the biochemical production of fuels and chemicals. Economically feasible large-scale implementation of the process requires operation at high solids loadings, i.e., biomass concentrations >15% (w/w). At increasing solids loadings, however, biomass forms a high viscosity slurry that becomes increasingly challenging to mix and severely mass transfer limited, which limits further addition of solids. To overcome these limitations, we developed a fed-batch process controlled by the yield stress and its changes during liquefaction of the reaction mixture. The process control relies on an in-line, non-invasive magnetic resonance imaging (MRI) rheometer to monitor real-time evolution of yield stress during liquefaction. Additionally, we demonstrate that timing of enzyme addition relative to biomass addition influences process efficiency, and the upper limit of solids loading is ultimately limited by end-product inhibition as soluble glucose and cellobiose accumulate in the liquid phase.


Subject(s)
Biotechnology/methods , Cellulose/metabolism , Batch Cell Culture Techniques , Biofuels , Biomass , Biotechnology/instrumentation , Cellobiose/chemistry , Cellobiose/metabolism , Cellulose/chemistry , Enzymes/chemistry , Enzymes/metabolism , Glucose/chemistry , Glucose/metabolism , Hydrolysis , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Rheology/instrumentation , Rheology/methods
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