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

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 lung...

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Autores principales: Lee, Wing-Hin, Loo, Ching-Yee, Traini, Daniela, Young, Paul M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822152/
https://www.ncbi.nlm.nih.gov/pubmed/33375181
http://dx.doi.org/10.3390/pharmaceutics13010009
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author Lee, Wing-Hin
Loo, Ching-Yee
Traini, Daniela
Young, Paul M.
author_facet Lee, Wing-Hin
Loo, Ching-Yee
Traini, Daniela
Young, Paul M.
author_sort Lee, Wing-Hin
collection PubMed
description 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.
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spelling pubmed-78221522021-01-23 Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment Lee, Wing-Hin Loo, Ching-Yee Traini, Daniela Young, Paul M. Pharmaceutics Article 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. MDPI 2020-12-22 /pmc/articles/PMC7822152/ /pubmed/33375181 http://dx.doi.org/10.3390/pharmaceutics13010009 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Wing-Hin
Loo, Ching-Yee
Traini, Daniela
Young, Paul M.
Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title_full Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title_fullStr Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title_full_unstemmed Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title_short Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment
title_sort development and evaluation of paclitaxel and curcumin dry powder for inhalation lung cancer treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822152/
https://www.ncbi.nlm.nih.gov/pubmed/33375181
http://dx.doi.org/10.3390/pharmaceutics13010009
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