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Article

Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment

1
Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur (RCMP UniKL), Ipoh 30450, Perak, Malaysia
2
Respiratory Technology, Woolcock Institute of Medical Research, Discipline of Pharmacology, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2037, Australia
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2021, 13(1), 9; https://doi.org/10.3390/pharmaceutics13010009
Submission received: 20 November 2020 / Revised: 15 December 2020 / Accepted: 21 December 2020 / Published: 22 December 2020

Abstract

Despite the effort to develop efficient targeted drug delivery for lung cancer treatment, the outcome remains unsatisfactory with a survival rate of 15% after 5 years of diagnosis. Inhalation formulation is an ideal alternative that could ensure the direct deposition of chemotherapeutics to the lungs. However, the design of an inhalable formulation that could simultaneously achieve a high local chemotherapeutic dose to the solid tumor and exert low pulmonary toxicities is a challenge, as the presence of 10–30% of chemotherapeutics in the lung is sufficient to induce toxicity. Therefore, this study aimed to develop a simple dry powder inhalation (DPI) formulation containing a model chemotherapeutic agent (paclitaxel, PTX) and a natural antioxidant (curcumin, CUR) that acts to protect healthy lung cells from injury during direct lung delivery. The co-jet-milling of CUR and PTX resulted in formulations with suitable aerosol performance, as indicated in the high fine particle fractions (FPF) (>60%) and adequate mass median aerodynamic diameter (MMAD). The CUR/PTX combination showed a more potent cytotoxic effect against lung cancer cells. This is evident from the induction of apoptosis/necrotic cell death and G2/M cell cycle arrests in both A549 and Calu-3 cells. The increased intracellular ROS, mitochondrial depolarization and reduced ATP content in A549 and Calu-3 cells indicated that the actions of CUR and PTX were associated with mitochondrial oxidative stress. Interestingly, the presence of CUR is crucial to neutralize the cytotoxic effects of PTX against healthy cells (Beas-2B), and this is dose-dependent. This study presents a simple approach to formulating an effective DPI formulation with preferential cytotoxicity towards lung cancer.
Keywords: lung cancer; paclitaxel; curcumin; dry powder inhalation lung cancer; paclitaxel; curcumin; dry powder inhalation

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MDPI and ACS Style

Lee, W.-H.; Loo, C.-Y.; Traini, D.; Young, P.M. Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment. Pharmaceutics 2021, 13, 9. https://doi.org/10.3390/pharmaceutics13010009

AMA Style

Lee W-H, Loo C-Y, Traini D, Young PM. Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment. Pharmaceutics. 2021; 13(1):9. https://doi.org/10.3390/pharmaceutics13010009

Chicago/Turabian Style

Lee, Wing-Hin, Ching-Yee Loo, Daniela Traini, and Paul M. Young. 2021. "Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment" Pharmaceutics 13, no. 1: 9. https://doi.org/10.3390/pharmaceutics13010009

APA Style

Lee, W.-H., Loo, C.-Y., Traini, D., & Young, P. M. (2021). Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment. Pharmaceutics, 13(1), 9. https://doi.org/10.3390/pharmaceutics13010009

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