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J Cancer 2024; 15(4):871-879. doi:10.7150/jca.90732 This issue Cite

Research Paper

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo

Paul Zarogoulidis^1,2✉, Dimitris Petridis³, Haidong Huang⁴, Chong Bai⁴, Georgia Pitsiou⁵, Dimitris Matthaios⁶, Eleni-Isidora Perdikouri⁷, Vasilis Papadopoulos⁸, Savvas Petanidis⁹, Christoforos Kosmidis², Wolfgang Hohenforst-schmidt¹⁰, Konstantinos Porpodis⁵, Nikos Kougas¹¹, Panagoula Oikonomou¹², Christina Nikolaou¹², Charalampos Charalampidis¹³, Chrysanthi Sardeli¹⁴

1. Pulmonary Department, General Clinic Euromedica, Thessaloniki, Greece.
2. 3rd University Surgery Department, ``AHEPA`` University Hospital, Thessaloniki, Greece.
3. Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece.
4. Department of Respiratory and Critical Care Medicine, Changhai Hospital, Navy Military Medical University, Shanghai, 200433, China.
5. Pulmonary Department, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Greece.
6. Oncology Department, General Hospital of Rhodes, Greece.
7. Oncology Department, General Hospital of Volos, Greece.
8. Oncology Department, University General Hospital of Larissa, Greece.
9. Department of Medicine, Laboratory of Medical Biology and Genetics, Aristotle University of Thessaloniki, Thessaloniki, Greece.
10. Sana Clinic Group Franken, Department of Cardiology / Pulmonology / Intensive Care / Nephrology, ''Hof'' Clinics, University of Erlangen, Hof, Germany.
11. Rheumatology Department, Ippokrateio University General Hospital, Thessaloniki, Greece.
12. Surgery Department, Democritus University of Thrace, Alexandroupolis, Greece.
13. Department of Pathology, University of Cyprus, Cyprus.
14. Department of Pharmacology & Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

✉ Corresponding author: Paul Zarogoulidis, M.D, Ph.D, Pulmonary Department, General Clinic Euromedica, Thessaloniki, Greece. Tel: 00306977271974; E-mail: pzarogcom.

Abstract

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept.

Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5μm in mass median aerodynamic diameter.

Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces.

Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Keywords: Paclitaxel, iloprost, sotatercept, jet-nebulizers, ultrasound nebulizers, pulmonary hypertension

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