Mechanistic modelling of targeted pulmonary delivery of dactinomycin iron oxide-loaded nanoparticles for lung cancer therapy / Shahd F. Al-Tarawneh, Eman Zmaily Dahmash, Hamad Alyami, Suha M. Abu-Doleh, Samer Al-Ali, Affiong Iyire, Rasha Abuthawabeh
Abstract With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1–2.5% dactinomycin and 0.5–0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect. Graphical Abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Pharmaceutical development and technology - 27(2022), 10, Seite 1057-1068 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Al-Tarawneh, Shahd F. [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
Chitosan |
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| Umfang: |
1 Online-Ressource (12 p) |
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| doi: |
10.1080/10837450.2022.2152047 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1–2.5% dactinomycin and 0.5–0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect. Graphical Abstract | ||
| 653 | |a Dactinomycin | ||
| 653 | |a nanoparticles | ||
| 653 | |a iron oxide | ||
| 653 | |a chitosan | ||
| 653 | |a sodium alginate | ||
| 653 | |a pulmonary drug delivery | ||
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| 700 | 1 | |a Alyami, Hamad |e verfasserin |4 aut | |
| 700 | 1 | |a Abu-Doleh, Suha M. |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Ali, Samer |e verfasserin |4 aut | |
| 700 | 1 | |a Iyire, Affiong |e verfasserin |4 aut | |
| 700 | 1 | |a Abuthawabeh, Rasha |e verfasserin |4 aut | |
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