10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
Abstract View
Hyperthermic Intracavitary Nanoaerosol Therapy (HINAT) - a Promising Approach to Treat Peritonealcarcinomatosis
Daniel Göhler, Stephan Große, LARS HILLEMANN, Alexander Bellendorf, Thomas A. Falkenstein, Mehdi Ouaissi, Jürgen Zieren, Michael Stintz, Urs Giger-Pabst, Technische Universität Dresden
Abstract Number: 39 Working Group: Aerosols in Medicine
Abstract Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an upcoming approach for the treatment of end-stage patients suffering on advanced peritonealcarcinomatosis. During conventional PIPAC (cPIPAC), a chemotherapeutic solution is aerosolized by a single-fluid nozzle (called micro injection pump MIP®) within the capnoperitoneum (i.e., inflated peritoneum with an overpressure of 1.6 kPa = 12 mmHg based on carbon dioxide). This kind of drug delivery (Solaß et al. 2012) circumvents several problems (e.g. adverse effects, systemic intolerance, ineffective drug delivery) accompanied to other established therapeutic methods (e.g. intraperitoneal resection, systemic chemotherapy or intraperitoneal liquid chemotherapy). But recently performed granulometric analyses on the aerosol of cPIPAC revealed a high optimization potential (Göhler et al. 2017a).
Thus a new PIPAC method (Göhler et al. 2017b), called Hyperthermic IntraCavitary NanoAerosol Therapy (HINAT), was developed to improve the homogeneity as well as the effectivity of drug deposition over the whole peritoneum. HINAT provides a nanometer-sized, unipolar-charged and hyperthermic aerosol for intracavitary use based on extracavitary aerosol generation (i.e. atomization by a two-fluid nozzle and immediate separation of coarse droplets) with subsequent aerosol conditioning.
The performance of both HINAT and cPIPAC were characterized in a comprehensive testing program, which comprised ex vivo granulometric analyses (laser diffraction spectrometry, time of flight spectrometry, differential electrical mobility analyses, condensation nuclei counting) for aerosol characterization, in post mortem swine analyses (scintigraphic peritoneography, fluorescence microscopy) for the characterization of spatial drug distribution and in-tissue drug penetration and in vivo proof of concept analyses in anesthetized swines.
Results show, that HINAT provides despite a hundreds times lower liquid drug flow rate a 25 times higher droplet generation rate than cPIPAC with a quasi-uniform deposition profile over the whole peritoneum. At a 3 times lower dose of a chemotherapeutic substance, the drug penetration depth of HINAT was found to be two times higher than the one for cPIPAC. Further information on the HINAT method and even more detailed results will be presented.
References Göhler D, Große S, Bellendorf A, Falkenstein TA, Ouaissi M, Zieren J, Stintz M, Giger-Pabst U. Hyperthermic intracavitary nano-aerosol therapy (HINAT) as improved approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC): Technical description, experimental validation and first proof of concept. Beilstein J. Nanotechnol., 2017, 8, 2729-2740.
Göhler D, Khosrawipour V, Khosrawipour T, Diaz-Carballo D, Falkenstein T, Zieren J, Stintz M, Giger-Pabst U. Technical description of the micro injection pump (MIP®) and granulometric characterization of the aerosol applied for Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Surg. Endosc., 2017, 31, 1778-178.
Solaß W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg. Endosc., 2012, 26, 1849-1855.