( 2017 2016)
Aerosol drug delivery/deposition in human lungs – In vitro experimental and in silico numerical simulation methods were used for the determination of the deposition distribution and deposition efficiency of aerosol drugs from pressurized metered dose inhalers and dry powder inhalers (widely utilized in the therapy of chronic pulmonary diseases) as a function of standard breathing parameters. The mass median aerodynamic diameter of the released particles was determined for different idealized inhalation waveforms, directly from the inhaler and after a realistic upper airway model. We found that the mass median aerodynamic diameter varies by a factor of 2 and decreases with increasing peak inspiratory flow and inhaled volume. It was measured to be approximately 10% lower after the upper airway. The stochastic lung deposition model was used to calculate the lung deposition of the medicament with each inhalation profile, taking into account the measured size distribution. We determined the minimum required inhalation flow for the examined dry powder inhalers for an acceptable level of lung deposition dose. Above 60 L/min peak inspiratory flow the lung deposition increases to above 50%, which may support a sufficient therapy. Our measurements showed that the length of the inhalation does not influence the lung deposition dose; peak inspiratory flow and inhaled volume are much more relevant factors. We presented a map of the deposition of the examined aerosol drug in the lung as a function of inhalation time and peak inspiratory flow (Fig.1.), which could be a useful tool for the doctors in the selection of the appropriate inhalation drug by knowing the correct inhalation parameters of the patient, these can help in the elaboration of personalized treatment.
Figure 1. The deposition efficiency map of a dry powder inhaler as a function of inhalation time (tin) and peak inspiratory flow (PIF).
Optical measurement techniques. — We have been involved in the development of prototype instruments for medical surgery applications based on short pulse and fibre lasers. The light scattering and absorption properties of model tissue materials were studied using different lasers and detection techniques, as well as the aerosol plume that is generated upon the interaction of intense laser light and model tissue materials. The spreading, concentration and optical properties of the smoke was studied using high-speed cameras and non-contact laser Doppler methods. We have been participating in the development of a new technology based on 3D metal printing with industrial partners.
Our previously developed optical method was utilized in a research project aimed at investigating the properties of absorbing aerosols (mineral dust - black carbon mixtures) in the Mediterranean region. The main aims of the project are to characterize the aging and mixing of light-absorbing aerosol layers, to assess the contribution of individual aerosol components to the radiative forcing of mixed absorbing aerosol layers, to implement complex particle morphologies in radiative forcing estimates, and to investigate potential links between the presence of absorbing particles, aerosol layer lifetime and removal. Our instrument was installed into a research aircraft monitoring the vertical and horizontal profile of aerosol contamination of the atmosphere in given trajectories.
The development of light sources of our patented expanded-beam imaging Spectro-ellipsometers are in progress in co-operation with the Institute for Technical Physics and Materials Science, Centre for Energy Research. Bio-photonic research was conducted to optimize the label-free, in-vivo fluorescence emission of different biological samples, according to their individual destruction thresholds in order to develop an optimal excitation laser source.
Aerosol drug delivery/deposition in human lungs. — The MMAD (mass median aerodynamic diameter) of the Symbicort® Turbuhaler dry powder inhaler (DPI) and the aerosol particle deposition in the upper airways was studied in case of different inhalation waveforms. For the detection of the aerosol size distribution, the Aerosol Particle Sizer (APS) Spectrometer was used. The effect of the breathing pattern on the MMAD was determined after the upper airways. With the help of the stochastic lung deposition model (SLDM), the amount of deposited particles in the lung was quantified. It was found that approximately 10% of the particles from the DPI deposit in the upper airways. The lung deposition of the drug from the DPI was calculated to be between 18 and 63% of the nominal dose, depending on the inhalation time and the peak inhalation flow.
Vibrational (Raman and infrared) spectroscopy based methods have been developed to determine the distribution of inhalation drugs (and other aerosols) in human airway replicas. The tested medication was introduced by metered dose inhaler into a realistic human lung tract prepared by 3D printing from computer tomographic data of human respiratory system. The deposited material was collected with silicon substrates attached to the hollow airway’s walls in different points. The analysis of the substrates was performed by Raman and infrared spectroscopic mapping of drug’s characteristic peak intensities over the surface. The method was verified by comparison with optical microscopic images recorded on the same surface area.
Study of optical properties of aerosols. — We have participated in the A-LIFE ERC project of the University of Vienna with PI Prof. Bernadett Weinzierl. The project is aimed at investigating the properties of absorbing aerosols (in particular mineral dust – black carbon (BC) mixtures) to characterize the aging and mixing of light-absorbing aerosol layers during their lifetime, to assess the contribution of individual aerosol components, in particular mineral dust and BC to the radiative forcing (RF) of mixed absorbing aerosol layers, to implement complex particle morphologies in RF estimates, and to investigate potential links between the presence of absorbing particles, aerosol layer lifetime and removal. We participated in the project by applying an optical method for the measurement of the optical and physical properties of ambient aerosols, which was developed by us in cooperation with the University of Vienna.
Optical thin film structures for advanced ultrafast applications. — We have continued our research concerning the development of optical thin film structures (high reflectors, output couplers, beam splitters, triple-band antireflective coatings etc.) for advanced femtosecond laser sources producing energetic light pulses in the near- and middle-infrared wavelength ranges. We have produced successfully sampling beam splitters on sapphire substrates for the French company Fastlite, working perfectly in their MIR laser system installed at ELI ALPS in Szeged already. We have developed new type of negative- or zero-dispersion multilayer mirror structures for our Japan partner also. The new laser mirror structures developed by us are very important in the development of new ultrafast high-power lasers which are able to shift the limits of the higher harmonic generation from the soft X-ray range to the hard X-ray range.
Optical measurement techniques serving the development of medical laser systems. — We have been involved in a project where the participants conduct research and development activities aiming at developing prototype instruments for medical surgery applications based on ultrashort pulse and fibre lasers. We have studied the light scattering and absorption properties of model tissue materials using different lasers and detection techniques. We have studied the surgical smoke that is generated upon the interaction of intense laser light and model tissue materials. In the frame of this study, we measured the size distribution of the surgical smoke with optical particle counter, aerodynamic particle counter and condensation particle counter, we measured the spread of the generated aerosols using laser Doppler anemometer, and collected samples with a cascade impactor for further analysis.
Aerosol drug delivery/deposition in human lungs. — An optical measurement method based on laser particle counting has been developed, which can be used as a replacement of the commonly used analytical methods. A new procedure was developed based on optical image processing for the determination of the amount of deposited particles on the catch plates of cascade impactors. We utilized this method for the investigation of the effect of the humidity on the size distribution of the inhaled drug particles.
A measurement setup was built and utilized to study the temporal development of the size distribution of the generated mist of pressurized metered dose inhalers (pMDI) which influence the spatial deposition distribution of the particles in the human airways. While the pump with the flow controller generates constant flow rate in a closed loop, the breath simulator and the mixing inlet ensures realistic breathing patterns at the pMDI device. An optical particle counter (OPC) isokinetically samples particles from the main flow providing the necessary dilution to avoid coincidence of particles in the measurement volume caused by the high concentration. Measurements were performed to determine the temporal variation of the size distribution of the aerosols generated by pMDI devices and also studied the effects of the synchronization problems commonly raised during the usage of these devices.
All of the above mentioned methods have their own advantages in terms of speed and sensitivity of the measurement. The established theoretical and experimental background and the elaborated methods and tools can be used widely not only for the investigation of aerosol drug delivery, but for studying the deposition properties of natural and toxic aerosols as well.
Study of optical properties of aerosols. — Optical aerosol instrumentation was utilized to identify the sources of aerosol contamination in the air of Budapest. The results of the size distribution and absorptivity measurements show clear correlation with weather conditions, indicating the differences between the locations in the neighbourhoods.
Optical thin-film structures consisting of nanoscale laminated layers. – We have continued our research towards the development of optical thin-film structures containing nanooptically thin layers for advanced applications in laser physics and information technology.
EXMET – Interferometric measurement methods. — The Michelson-type interferometer which was developed in the previous phase of this project was utilized for plasma diagnostics. The properties of the plasma generated in rubidium vapors by intense femtosecond laser pulses were studied using interferometry scheme in coaxial arrangement with the ionizing laser beam (Fig. 1.). This method was found to be a useful tool for laser plasma diagnostics and may complement the absorption spectroscopy methods. It can be even utilized with laser sources that produce less intense measuring beam because of the intrinsic nature of interferometry.
Figure 1. Schematic measurement setup for studying the dynamics of an Rb plasma generated by ultra-short laser pulses
Development of an imaging optical inspection device with a pinhole camera. – In cooperation with the Institute of Technical Physics and Material Sciences of Centre for Energy Research, an upgraded version of our “Imaging Optical Inspection Device With A Pinhole Camera” was developed. The aim was to increase the size of the measurable targets. It requires a significant increase of brightness of the special „point like” light source, the speed and range of precisely controlled target movement, and data processing. The unit was successfully installed in the clean-room of IISB (Erlangen, Germany). (For details see: http://www.ellipsometry.hu/)
Service laboratory for optical measurements. — We have continued the utilization of our surface profiler based on white light interferometry. We have performed aerosol measurements by optical and spectroscopic methods in the frame of academic cooperations and industrial contracts.