Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.

Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor

Hypoxia commonly occurs within tumours and is a major cause of radiotherapy resistance. Clinical outcomes could be improved by locating and selectively increasing the dose delivered to hypoxic regions. Here we describe a miniature implantable sensor for real-time monitoring of tissue oxygenation that could enable this novel treatment approach to be implemented. The sensor uses a solid-state electrochemical cell that was microfabricated at wafer level on a silicon substrate, and includes an integrated reference electrode and electrolyte membrane. It gave a linear response to oxygen concentration, and was unaffected by sterilisation and irradiation, but showed susceptibility to biofouling. Oxygen selectivity was also evaluated against various clinically relevant electroactive compounds. We investigated its robustness and functionality under realistic clinical conditions using a sheep model of lung cancer. The sensor remained functional following CT-guided tumour implantation, and was sufficiently sensitive to track acute changes in oxygenation within tumour tissue.

Multilayer Polymeric Nano composite Membrane for Oxygen Separation

Air separation is a process of separating primary components from the atmospheric air. Development of membrane technologies plays a key role in air separation. Multi-layer polymeric nanocomposite membranes have been developed by a novel technique using Polyacrylonitrile (PAN) and cellulose acetate (CA) along with nano silica particles (SiO2) to obtain a higher oxygen selectivity and permeability. For the construction of the multilayer membrane, the Box-Behnken design has been used by employing three independent variables namely PAN Electro spinning time, the SiO2 percentage in the PAN polymer and CA/PEG polymer concentration. The developed membranes have been characterized for its surface morphology and physical properties. Along with the analysis of compound desirability, the results were also subject to statistical analysis in order to form regression equations. The electro spun fiber diameter increases along with the concentration of SiO2 nanoparticles and the range is from 50 nm to 400 nm. Moreover, the maximum pore size on the surface of the membrane lies between 200 to 400 nm whereas the maximum percentage of oxygen purity obtained is 48 with the permeate flux of 5.45 cm3/cm2/min.