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https://hdl.handle.net/1889/4299
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DC Field | Value | Language |
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dc.contributor.advisor | Sonvico, Fabio | - |
dc.contributor.advisor | Colombo, Paolo | - |
dc.contributor.author | Quarta, Eride | - |
dc.date.accessioned | 2021-04-22T13:55:29Z | - |
dc.date.available | 2021-04-22T13:55:29Z | - |
dc.date.issued | 2020-04 | - |
dc.identifier.uri | https://hdl.handle.net/1889/4299 | - |
dc.description.abstract | The aim of this work was to pharmaceutically develop an innovative nanomedicine consisting in highly respirable microparticulate dry powder (dpCaPs) able to embed and release Calcium Phosphate nanoparticles (CaPs) loaded with mimetic peptide or microRNA to restore the cardiac function. The microparticles, embedding therapeutic nanoparticles delivered by inhalation in deep lung, release the CaPs by carrier dissolution and target the hearth by translocation to pulmonary vein blood. Spray drying technique transformed the nanoparticle dispersion in inhalable microparticles. Mannitol, as water soluble carrier, was used for microparticle construction. A DoE was applied for understanding the effect of the composition and process parameters on selected quality attributes of dpCaPs. In vitro respirability was performed using the novel medium resistance Nemera prototype device. The DoE study revealed that the powder having the ratio CaPs/mannitol 1:4 exhibited the best aerodynamic performance for lung deposition and CaP release. The emitted dose was >85%, the FPF >80%. Microparticles had a spherical shape, rough surface and low density. The high fraction (i.e. 50%) of extra-fine particles (< 2µm) promotes the CaP deep lung deposition at alveolar region and translocation to the hearth. The CaP nanoparticles and microparticles were successfully produced at pilot scale. In vitro evaluation found that dpCaPs were not toxic for human lung alveolar epithelial cells and macrophages and did not induce cytokine release. The microparticles embedding loaded CaPs tested on murine HL-1 cardiac cells allowed the peptide internalization in the myocytes with a dose dependent mechanism. Finally, the dpCaPs pulmonary in vivo administered to diseased mini pigs were able to restore the normal heart contractility. | en_US |
dc.language.iso | Inglese | en_US |
dc.publisher | Università degli Studi di Parma. Dipartimento di Scienze degli alimenti e del farmaco | en_US |
dc.relation.ispartofseries | Dottorato di ricerca in Scienze del farmaco, delle biomolecole e dei prodotti per la salute | en_US |
dc.rights | © Eride Quarta, 2021 | en_US |
dc.rights | Attribuzione - Non commerciale - Non opere derivate 3.0 Italia | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/it/ | * |
dc.subject | Microparticles embedding nanoparticles | en_US |
dc.subject | Calcium phosphate nanoparticles | en_US |
dc.subject | heart targeting | en_US |
dc.subject | pulmonary delivery | en_US |
dc.title | Inhalation drug products of loaded calcium phosphate nanoparticles for heart targeting | en_US |
dc.type | Doctoral thesis | en_US |
dc.subject.miur | CHIM/09 | en_US |
Appears in Collections: | Scienze del farmaco, delle biolomolecole e dei prodotti per la salute. Tesi di dottorato |
Files in This Item:
File | Description | Size | Format | |
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Final2020_33_ErideQuarta.pdf Restricted Access | Final Report_Eride Quarta | 559.57 kB | Adobe PDF | View/Open Request a copy |
PhD Thesis_Eride Quarta.pdf | 9.59 MB | Adobe PDF | View/Open |
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