Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity

Amira Motawea,1 Dalia Alsaied Moustafa Ahmed,2 Ahmed A El-Mansy,3,4 Noha Mohamed Saleh1 1Pharmaceutics Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Department...

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Autores principales:	Motawea A, Ahmed DAM, El-Mansy AA, Saleh NM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	amiodarone pulmonary toxicity plga nanoparticles bsa cytotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c60470ee925f4e9bbf87f45959e04f8e
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spelling	oai:doaj.org-article:c60470ee925f4e9bbf87f45959e04f8e2021-12-02T15:05:54ZCrucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity1178-2013https://doaj.org/article/c60470ee925f4e9bbf87f45959e04f8e2021-07-01T00:00:00Zhttps://www.dovepress.com/crucial-role-of-plga-nanoparticles-in-mitigating-the-amiodarone-induce-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Amira Motawea,1 Dalia Alsaied Moustafa Ahmed,2 Ahmed A El-Mansy,3,4 Noha Mohamed Saleh1 1Pharmaceutics Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Department of Histology, Horus University, Dumyat al Jadidah, EgyptCorrespondence: Noha Mohamed Saleh Email nunu_ramy@mans.edu.egBackground: Amiodarone (AMD) is a widely used anti-arrhythmic drug, but its administration could be associated with varying degrees of pulmonary toxicity. In attempting to circumvent this issue, AMD-loaded polymeric nanoparticles (AMD-loaded NPs) had been designed.Materials and Methods: AMD was loaded in NPs by the nanoprecipitation method using two stabilizers: bovine serum albumin and Kolliphor® P 188. The physicochemical properties of the AMD-loaded NPs were determined. Among the prepared NPs, two ones were selected for further investigation of spectral and thermal analysis as well as morphological properties. Additionally, in vitro release patterns were studied and kinetically analyzed at different pH values. In vitro cytotoxicity of an optimized formula (NP4) was quantified using A549 and Hep-2 cell lines. In vivo assessment of the pulmonary toxicity on Sprague Dawley rats via histopathological and immunohistochemical evaluations was applied.Results: The developed NPs achieved a size not more than 190 nm with an encapsulation efficiency of more than 88%. Satisfactory values of loading capacity and yield were also attained. The spectral and thermal analysis demonstrated homogeneous entrapment of AMD inside the polymeric matrix of NPs. Morphology revealed uniform, core-shell structured, and sphere-shaped particles with a smooth surface. Furthermore, the AMD-loaded NPs exhibited a pH-dependent and diffusion-controlled release over a significant period without an initial burst effect. NP4 demonstrated a superior cytoprotective efficiency by diminishing cell death and significantly increasing the IC50 by more than threefold above the pure AMD. Also, NP4 ameliorated AMD-induced pulmonary damage in rats. Significant downregulation of inflammatory mediators and free radicle production were noticed in the NP4-treated rats.Conclusion: The AMD-loaded NPs could ameliorate the pulmonary injury induced by the pure drug moieties. Cytoprotective, anti‐fibrotic, anti-inflammatory, and antioxidant properties were presented by the optimized NPs (NP4). Future studies may be built on these findings for diminishing AMD-induced off-target toxicities.Keywords: amiodarone, pulmonary toxicity, PLGA, nanoparticles, BSA, cytotoxicityMotawea AAhmed DAMEl-Mansy AASaleh NMDove Medical Pressarticleamiodaronepulmonary toxicityplgananoparticlesbsacytotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 4713-4737 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amiodarone pulmonary toxicity plga nanoparticles bsa cytotoxicity Medicine (General) R5-920
spellingShingle	amiodarone pulmonary toxicity plga nanoparticles bsa cytotoxicity Medicine (General) R5-920 Motawea A Ahmed DAM El-Mansy AA Saleh NM Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
description	Amira Motawea,1 Dalia Alsaied Moustafa Ahmed,2 Ahmed A El-Mansy,3,4 Noha Mohamed Saleh1 1Pharmaceutics Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Department of Histology, Horus University, Dumyat al Jadidah, EgyptCorrespondence: Noha Mohamed Saleh Email nunu_ramy@mans.edu.egBackground: Amiodarone (AMD) is a widely used anti-arrhythmic drug, but its administration could be associated with varying degrees of pulmonary toxicity. In attempting to circumvent this issue, AMD-loaded polymeric nanoparticles (AMD-loaded NPs) had been designed.Materials and Methods: AMD was loaded in NPs by the nanoprecipitation method using two stabilizers: bovine serum albumin and Kolliphor® P 188. The physicochemical properties of the AMD-loaded NPs were determined. Among the prepared NPs, two ones were selected for further investigation of spectral and thermal analysis as well as morphological properties. Additionally, in vitro release patterns were studied and kinetically analyzed at different pH values. In vitro cytotoxicity of an optimized formula (NP4) was quantified using A549 and Hep-2 cell lines. In vivo assessment of the pulmonary toxicity on Sprague Dawley rats via histopathological and immunohistochemical evaluations was applied.Results: The developed NPs achieved a size not more than 190 nm with an encapsulation efficiency of more than 88%. Satisfactory values of loading capacity and yield were also attained. The spectral and thermal analysis demonstrated homogeneous entrapment of AMD inside the polymeric matrix of NPs. Morphology revealed uniform, core-shell structured, and sphere-shaped particles with a smooth surface. Furthermore, the AMD-loaded NPs exhibited a pH-dependent and diffusion-controlled release over a significant period without an initial burst effect. NP4 demonstrated a superior cytoprotective efficiency by diminishing cell death and significantly increasing the IC50 by more than threefold above the pure AMD. Also, NP4 ameliorated AMD-induced pulmonary damage in rats. Significant downregulation of inflammatory mediators and free radicle production were noticed in the NP4-treated rats.Conclusion: The AMD-loaded NPs could ameliorate the pulmonary injury induced by the pure drug moieties. Cytoprotective, anti‐fibrotic, anti-inflammatory, and antioxidant properties were presented by the optimized NPs (NP4). Future studies may be built on these findings for diminishing AMD-induced off-target toxicities.Keywords: amiodarone, pulmonary toxicity, PLGA, nanoparticles, BSA, cytotoxicity
format	article
author	Motawea A Ahmed DAM El-Mansy AA Saleh NM
author_facet	Motawea A Ahmed DAM El-Mansy AA Saleh NM
author_sort	Motawea A
title	Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
title_short	Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
title_full	Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
title_fullStr	Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
title_full_unstemmed	Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity
title_sort	crucial role of plga nanoparticles in mitigating the amiodarone-induced pulmonary toxicity
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c60470ee925f4e9bbf87f45959e04f8e
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Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity

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