J Cancer 2020; 11(6):1308-1314. doi:10.7150/jca.39097

Research Paper

Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure

Tanja Khosrawipour1,2✉*, Justyna Schubert3*, Joanna Kulas4, Pawel Migdal5, Mohamed Arafkas6, Jacek Bania3, Veria Khosrawipour1

1. Division of Colorectal Surgery, Department of Surgery, University of California, Irvine, California, USA.
2. Department of Surgery (A), University-Hospital Düsseldorf, Düsseldorf, Germany
3. Department of Food Hygiene and Consumer Health Protection, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
4. Department of Biochemistry and Molecular Biology, Faculty of Veterinary Sciences, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
5. Department of Environment, Hygiene and Animal Welfare, University of Environmental and Life Sciences, Wroclaw, Poland.
6. Department of Plastic Surgery, Ortho-Klinik Dortmund, Dortmund, Germany.
* Both authors should be considered as first author.

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Citation:
Khosrawipour T, Schubert J, Kulas J, Migdal P, Arafkas M, Bania J, Khosrawipour V. Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure. J Cancer 2020; 11(6):1308-1314. doi:10.7150/jca.39097. Available from http://www.jcancer.org/v11p1308.htm

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Abstract

Background: Nanocrystallization is a promising field for the development of new drugs. This study aims to present the use of nanocrystallization via intraperitoneal nanoaerosol therapy (INAT) for the treatment of peritoneal metastases.

Methods: A continuous aerosol generation device was used to aerosolize a highly concentrated doxorubicin solution within a dry CO2 environment. The produced nanoaerosol was directed into an ex vivo abdominal model and collision of aerosol particles with placed samples was subject to further analysis via scanning-electron microscopy (SEM). SEM detected structural changes of particles caused by migration to different locations.

Results: It was possible to visualize the contact of doxorubicin aerosol particles with the surface. Larger particles as well as particles closer to the aerosol generation chamber collided with the glass sample creating liquid drops, while smaller particles with more distance to the aerosol chamber collided as highly concentrated nanocrystals. The amount of nanocrystal particles outweighed the amount of fluid aerosol particles by far.

Conclusions: Under optimal conditions, the formation of nanocrystals via aerosol creation device is possible. While a wide range of possible applications of nanocrystals is conceivable, surface coating with drug particles is especially interesting as it may serve as an alternative to conventional liquid intraperitoneal chemotherapy. Further studies are required to investigate nanocrystallization of chemotherapeutic solutions as well as its physical and pharmacological properties and side effects.

Keywords: electron microscopy, pressurized intra-peritoneal aerosol chemotherapy (PIPAC), peritoneal metastases, nanoparticles, chemotherapy