Conor S. Burke

Magnetic core-shell nanoparticles for drug delivery by nebulization

BackgroundAerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe3O4 magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.ResultsAverage particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 μg/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.ConclusionWe have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route.

Development of a compact optical sensor for real-time, breath-by-breath detection of oxygen

The detection of oxygen in breath is of central importance to investigations of metabolism and respiration in both clinical and athletic performance monitoring applications. This paper reports the development of a portable, lightweight optical oxygen sensor that is intended to provide a breath oxygen monitoring solution that is deployable outside a laboratory environment. The sensing methodology is based on the detection of changes in the fluorescence emission of an oxygen-sensitive fluorescent dye. The novelty of the system stems from the humidity-insensitive nature of the oxygen sensor, the highly efficient and compact optical configuration and the use of a novel, wearable control unit based on DSP circuitry. These components combine to provide a portable breath oxygen monitor that can detect changes in the in-breath O(2) concentration profile in real-time over a broad range of breathing rates in situations of both rest and exercise. The reported system is expected to have a significant impact on point-of-care (POC) breath-based diagnostics and high performance athletic monitoring.

Breath-by-breath measurement of oxygen using a compact optical sensor

We report on the development of a novel optical oxygen sensor for breath monitoring applications using the technique of phase fluorometry. The principal design criteria are that the system be compact, lightweight, and employ a disposable sensing element (while performing competitively with current commercial analyzers). The oxygen-sensitive, luminescent ruthenium complex Ru[dpp](3)(2+) is encapsulated in a sol-gel matrix and deposited onto a custom-designed, polymer sensor chip that provides significantly improved luminescence capture efficiency. The performance of the sensor module is characterized using a commercially available lung simulator. A resolution of 0.03% O(2) is achieved, which compares well with commercial breath monitoring systems and, when combined with its immunity to humidity and ability to respond effectively across a broad range of breathing rates, makes this device an extremely promising candidate for the development of a practical, low-cost biodiagnostic tool.

Design and fabrication of enhanced polymer waveguide platforms for absorption-based optical chemical sensors

The development of mass-producible polymer waveguide chips as enhanced platforms for absorption-based optical chemical sensors employing thin colorimetric films is reported here. The chip design is based on a previously reported theoretical study relating to the optimization of the sensitivity of optical absorption-based sensors employing a single reflection configuration. Here, the theoretical analysis is extended to a multiple reflection configuration in order to determine the dependence of sensitivity on interaction length, and the findings are investigated experimentally. The existence of the optimum sensing conditions predicted by theory is demonstrated empirically by examining the pH response of polymer waveguide platforms coated with a sol–gel derived sensing layer doped with a colorimetric pH indicator. This work has major implications for the fabrication of miniaturized, disposable sensor platforms that demonstrate enhanced sensitivity when compared with those utilizing more commonly employed optical configurations.

Optimization of absorption-based optical chemical sensors that employ a single-reflection configuration.

An optimization strategy for a generic absorption-based optical chemical sensor that employs a single-reflection planar configuration is reported. A theoretical model describing the sensor sensitivity is presented and verified experimentally. It is shown that optimum sensitivity is not achieved with an evanescent-wave sensing technique but with a configuration in which the interrogating light propagates within the sensing layer. Moreover, an optimization strategy based on identification of an optimized reflection angle is described. This analysis provides an optimization strategy that is extendable to multimode waveguide platforms. The predictions of the model are used in the design of a prototype LED-based sensor system. The performance of this system is examined, and the results are compared with alternative absorption-based sensor configurations.

A novel camera phone-based platform for quantitative fluorescence sensing

We describe a novel camera phone-based optical sensing platform capable of real-time quantitative fluorescence-based measurements. The platform employs the phones camera as a photodetector in a non-imaging optical configuration that simultaneously detects fluorescence from a number of sensor spots on a disposable optical sensor chip. The platform combines the functionality of the camera with the phones data-processing capabilities to facilitate on-phone analysis of detected fluorescence intensity. It is envisaged that such a platform will have significant potential in application areas such as environmental monitoring and healthcare where there is a growing demand for decentralized diagnostics using low-cost, portable devices, particularly in remote or low-resource environments.

Enhanced polymer waveguide platforms for absorption-based optical chemical sensors

The development of polymer waveguide chips as platforms for optimized absorption-based optical chemical sensors is reported here. The chips were designed in accordance with theoretical predictions published elsewhere relating to the optimization of the sensitivity of optical absorption-based sensors. The waveguides were fabricated by micro-injection moulding and coated with a colourimetric, sol-gel-derived sensing layer. They were then incorporated into a compact, LED-based sensing device for the detection of gaseous NH3. Results presented here demonstrate comparable sensitivity to more complex systems reported to date.