Current Research

Quantification of (airborne) particle deposition on the "entry port" in the human nose for CNS active drugs

 
The olfactory nerve in the upper region of the human nose may function as an "entry port" for CNS treatment drugs, such as i.e. biopharmaceuticals as well as oxime drugs (for treatment of poisoning by organophosphorous compounds such as paraoxon). Over the last few decades this alternative route was followed up by a number of research groups. Emerging data suggest the presence of two "bottlenecks": the transport a. of aerosol particles from the nose inlet to the olfactory nerve and b. of the active ingredient along the olfactory nerve pathway (see the following figure). The research project carried out in Biberach at the University of Applied Sciences focuses on the first bottleneck by investigating the transport of aerosol particles to the surface of the olfactory region (future dosage form as a nasal spray or a pocket inhaler).

Figure: The bottlenecks for nasally inhaled CNS active drugs (left) and deposited particles on the olfactory nerve, CFD (computational fluid dynamics) results (right).

In order to pursue this innovative route, it is necessary to measure and quantify the particles which reach the olfactory nerve. Process engineering methods offer an adequate solution to model the aerosol flow as well as the separation efficiency of deposited particles employing numerical (CFD simulations) and experimental methods with model aerosols such as water droplets or silica particles (SiO2).
 
The following results were obtained in previous studies carried out in cooperation with the ZHAW Life Sciences und Facility Management, Switzerland (Prof. Eibl) /A.1/ and more recently with the UZWR of the university of Ulm (Dr. Simon) /A.2 - A.6/.

Figure: Comparison of experimental and numerical (CFD simulation) "deposited particles" in a human nose model.

Furthermore a promising and new approach is the next intended target: A bionic concept in aerosol drug delivery leads to high separation efficiencies in the low accessible region of the nose, the olfactory nerve /A.7/.

 /A.1/ Steinicke, Malte, Master-Thesis, Beitrag zur Optimierung relevanter Einflussgrößen eines medizinischen Aerosols zur effizienten Abscheidung am olfaktorischen Epithelium mittels Computational Fluid Dynamics, Erstbetreuer: Schafmeister, A.

 /A.2/ Stuetzle, M., Steinicke, M., Eibl, D., Schafmeister, A. Intranasal aerosol drug delivery within a human nose model, Aerosol Technology, Karlsruhe 2014

/A.3/ Steinicke, M., Stützle, M., Werner, S., Eibl, D., Schafmeister, A., Deposition of particles in the human nose employing Computational Fluid Dynamics (CFD) simulation, , Biotech 2013, Wädenswil Schweiz, Juni 2013

/A.4/ Engelhardt, L., Simon, U., Stützle, M., Schafmeister, A.: Simulation und Validierung von Luft- und Partikelströmungen durch die Nase. In Proc. of ACUM 2015, Bremen.

/A.5/ Engelhardt L, Röhm M, Mavoungou Ch, Schindowski K, Schafmeister A, Simon U: First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals. Pharmaceutical Research, published Online First, 2016.

/A.6/ Stützle M, Carle S, Engelhardt L, Simon U, Schafmeister A, Mavoungou C, Schindowski K. (2015), Protein aerosol for intranasal nose to brain (N2B) delivery. BMC Proceedings 9 (Suppl 9): O11

/A.7/ DE 10 2015 122 405.4, Annette Schafmeister, Verfahren und Vorrichtung zum Einbringen medizinischer Wirkstoffe in das Zentralnervensystem des Menschen, eingereicht im Deutschen Patentamt am 29.12.2015.
 

A technical approach on precise determination of minimal mass of deposited airborne particles

 
A novel technique (principle is proofed) is based on a highly sensitive and robust approach to determine the mass of airborne particles deposited e.g. on a cell layer of an in vitro exposure unit /B.1/. This device enables accurate online and in situ measurements in order to collect valid information and data on dose-response-relationships e.g. in toxicity investigations /B.2/.

The measuring principle is based on the physical effect of changing the dielectric medium in-between an electrical condenser resulting in a change of the capacity. There are several advantages in measuring such a change of capacity due to an increase in mass. Firstly, the capacitive changes can be detected in the femto ampere region, which allows the recording of small mass increases. Secondly, the physics of dielectrics prognoses a linear dependency of the capacity change from the collected particle mass that affords only a simple calibration procedure. Many industrial measurement techniques take already advantage of this physical fact /B.3/.

In order to improve in vitro test methods regarding validity and automation with aerosol particles this method may allow a rapid online measurement of very low particle masses (broad application field in vitro toxicity tests inhalable and respirable dust and haze in the course of the realization of the CLP- und REACH regulation).

/B.1/ DE102011056045 A1, Annette Schafmeister, Vorrichtung zur Massenbestimmung von Aerosolpartikeln, Juni 2013

/B.2/ Aufderheide M, Scheffler S, Möhle N, Halter B, Hochrainer D. In-vitro cell exposure for the assessment of nanoparticle toxicity in the lung – A dialog between aerosol science and biology. 2011; Journal of Aerosol Science 42:688-692

/B.3/ Flagon, Richard C. 1998, Aerosol Science and Technology, Vol. 28(4): 301-380

SCIENTIFIC TOOLS AND EXPERTISE IN PARTICLE ENGINEERING AND AEROSOL TECHNOLOGY

Services

  • Technical consulting in the areas of particle technology and particle engineering
  • Scalable particle generation systems and measuring instruments for their characterization.
Lab Equipment

A wide selection of instruments with a measuring range from the nm to the µm scale:
  • Malvern, Spraytec: Malvern Instrument's Spraytec laser diffraction system allows measurement of spray particle and spray droplet size distributions in real-time for more efficient product development of sprays and aerosols.
  • TSI, Nanoscan: The NanoScan SMPS opens the door to routine nanoparticle size measurements and enables to collect valuable nanoparticle size data from more sites.
  • TSI, OPS: Optical Particle Sizer 3330 (OPS) is a light, portable unit that provides fast and accurate measurement of particle concentration and particle size distribution using single particle counting technology and uses state-of-the-art optics with 120° light collection and sophisticated electronics processing resulting in precision, high quality data.
  • Aerosol Particle Filters systems for gravimetric determination of particle mass concentration (µg/l].
 
Several aerosol generation techniques:
  • Aeroneb Pro
  • Suspension to Aerosol generator (with drying line)
  • two-substance-nozzle
  • fluidized bed aerosol generator
  • Mixing chamber