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Tytuł:
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Development and characterization of inhalable transferrin functionalized amodiaquine nanoparticles - Efficacy in Non-Small Cell Lung Cancer (NSCLC) treatment.
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Autorzy:
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Parvathaneni V; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Shukla SK; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Kulkarni NS; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Gupta V; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA. Electronic address: .
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Źródło:
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International journal of pharmaceutics [Int J Pharm] 2021 Oct 25; Vol. 608, pp. 121038. Date of Electronic Publication: 2021 Aug 23.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
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MeSH Terms:
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Amodiaquine*/therapeutic use
Carcinoma, Non-Small-Cell Lung*/drug therapy
Lung Neoplasms*/drug therapy
Nanoparticles*
A549 Cells ; Cell Line, Tumor ; Drug Delivery Systems ; Humans ; Transferrin
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Contributed Indexing:
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Keywords: Amodiaquine; Cancer targeting; Conjugation; Nanoparticles; Repurposing; Transferrin
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Substance Nomenclature:
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0 (Transferrin)
220236ED28 (Amodiaquine)
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Entry Date(s):
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Date Created: 20210826 Date Completed: 20211012 Latest Revision: 20220531
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Update Code:
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20240104
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DOI:
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10.1016/j.ijpharm.2021.121038
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PMID:
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34438008
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New drug discovery and development processes encounter significant challenges including requirement of huge investments and lengthy time frames especially in cancer research field. Repurposing of old drugs against cancer provides a possible alternative while associated scale-up complexities with production of nanoparticles at industrial scale could be overcome by using a scalable nanoparticle technique. We previously described use of polymeric nanoparticles for inhaled delivery of amodiaquine (AQ) for non-small cell lung cancer (NSCLC) treatment. In this study, targeting potential of transferrin ligand conjugated inhalable AQ-loaded nanoparticles (Tf-AMQ NPs) was investigated against NSCLC. Tf-AMQ NP (liquid formulation) demonstrated an aerodynamic diameter of 4.4 ± 0.1 µm and fine particle fraction of 83.2 ± 3.0%, representing AQ deposition in the respirable region of airways. Cytotoxicity studies in NSCLC cell line with overexpressed transferrin receptors shown significant reduction in IC 50 values with Tf-decorated AQ-loaded nanoparticles compared to AQ or non-targeted NPs, along with significant apoptosis induction (caspase assay) and reduced % colony growth in A549 and H1299 cells with Tf-AMQ NP. Furthermore, 3D spheroid studies (~7-fold reduction in spheroid volume compared to AMQ NPs) explained efficiency of conjugated nanoparticles in penetrating tumor core, and growth inhibition. AQ's autophagy inhibition ability significantly increased with nanoparticle encapsulation and transferrin conjugation. In conclusion, amodiaquine can be an assuring candidate for repurposing to consider for NSCLC treatment while delivering inhalable transferrin conjugated nanoparticles developed using a scalable HPH process to the target site, thus reducing the dose, side effects.
(Copyright © 2021 Elsevier B.V. All rights reserved.)