Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery

Eman Zmaily Dahmash; Nour Radwan Achkar; Dalia Khalil Ali; Qais Jarrar; Affiong Iyire; Shereen M. Assaf; Hamad Alyami

doi:10.1038/s41598-024-59588-1

Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery

Eman Zmaily Dahmash^*, Nour Radwan Achkar, Dalia Khalil Ali, Qais Jarrar, Affiong Iyire, Shereen M. Assaf, Hamad Alyami

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Original language	English
Article number	9845
Number of pages	16
Journal	Scientific Reports
Volume	14
Issue number	1
Early online date	29 Apr 2024
DOIs	https://doi.org/10.1038/s41598-024-59588-1
Publication status	Published - 29 Apr 2024

Bibliographical note

Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

Data Access Statement

All data generated or analysed during this study are included in this published article.

Keywords

Dry powder inhaler
Tyrosine-based poly (ester amide)
Interfacial polycondensation
Salmeterol xinafoate
Fluticasone propionate

Access to Document

10.1038/s41598-024-59588-1

Dahmash et al Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery
Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/
Final published version, 2.05 MBLicence: CC BY 4.0

Cite this

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abstract = "Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.",

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Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery

Abstract

Bibliographical note

Data Access Statement

Keywords

Access to Document

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