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

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 CO 2 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.

Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)

“…Data on electrostatic augmentation is scarce, and the potential of electrostatic PIPAC is unknown. Analyzing the effects of electrostatic precipitation combined with the applied aerosol itself is quite a challenge, and while ongoing studies present new locations and various applications for chemoaerosol [39,40], there is an ongoing effort to understand the applied chemoaerosol itself [39,41]. e application of heat in IPC is well studied.…”

“…erefore, it remains unclear if heat has a role in PIPAC. Despite these limitations, concepts based on basic physical principles like heat, electrostatic effects, changing physical properties of applied substances [39], or mechanic alteration [43] of the biological surface have gained more interest recently as they seem to have more potential than initially expected.…”

Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives

“…More precisely, thanks to an airstream travel, aerosols have time to crystallize. These nano-crystallized chemotherapies lead to higher tissue penetration rates that surpass that of PIPAC [ 76 ].…”

The Onset of In-Vivo Dehydration in Gas -Based Intraperitoneal Hyperthermia and Its Cytotoxic Effects on Colon Cancer Cells

“…In PIPAC, a fluid chemosolution is aerosolized and injected into the abdominal cavity covering the abdominal compartment. In fact, PIPAC has shown some positive results ( 12 , 13 ) and several attempts have been made to improve ( 14 , 15 ) and extend ( 16 ) its application. Nevertheless, the use of PIPAC in the clinical setting does not seem to fundamentally change patient outcome.…”