Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss

Xiaohua Li,1 Yanchun Wang,2 Feilong Xu,1 Feng Zhang,1 Ying Xu,3 Lei Tang,3 Thomas J Webster4 1Department of Otolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Department of Chinese Medicine, Henan Provincial People&rsqu...

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Autores principales:	Li X, Wang Y, Xu F, Zhang F, Xu Y, Tang L, Webster TJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	artemisinin mpeg-pcl nanoparticles gelma hydrogel hearing loss gentamicin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/68a77a8f922a45daa4a79d363158397b
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spelling	oai:doaj.org-article:68a77a8f922a45daa4a79d363158397b2021-12-02T08:29:01ZArtemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss1178-2013https://doaj.org/article/68a77a8f922a45daa4a79d363158397b2020-06-01T00:00:00Zhttps://www.dovepress.com/artemisinin-loaded-mpeg-pcl-nanoparticle-based-photosensitive-gelatin--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaohua Li,1 Yanchun Wang,2 Feilong Xu,1 Feng Zhang,1 Ying Xu,3 Lei Tang,3 Thomas J Webster4 1Department of Otolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Department of Chinese Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 4Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USACorrespondence: Xiaohua Li; Thomas J Webster Tel +86013837160836; Tel +1 617 373 6585Email kfxiaohua@126.com; th.webster@neu.eduObjective: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ϵ-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study.Materials and Methods: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology.Results: The zeta potential of the mPEG-PCL-ART-NPs was about − 38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM.Conclusion: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.Keywords: artemisinin, mPEG-PCL nanoparticles, GelMA hydrogel, hearing loss, gentamicinLi XWang YXu FZhang FXu YTang LWebster TJDove Medical Pressarticleartemisininmpeg-pcl nanoparticlesgelma hydrogelhearing lossgentamicinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4591-4606 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	artemisinin mpeg-pcl nanoparticles gelma hydrogel hearing loss gentamicin Medicine (General) R5-920
spellingShingle	artemisinin mpeg-pcl nanoparticles gelma hydrogel hearing loss gentamicin Medicine (General) R5-920 Li X Wang Y Xu F Zhang F Xu Y Tang L Webster TJ Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
description	Xiaohua Li,1 Yanchun Wang,2 Feilong Xu,1 Feng Zhang,1 Ying Xu,3 Lei Tang,3 Thomas J Webster4 1Department of Otolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Department of Chinese Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 4Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USACorrespondence: Xiaohua Li; Thomas J Webster Tel +86013837160836; Tel +1 617 373 6585Email kfxiaohua@126.com; th.webster@neu.eduObjective: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ϵ-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study.Materials and Methods: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology.Results: The zeta potential of the mPEG-PCL-ART-NPs was about − 38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM.Conclusion: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.Keywords: artemisinin, mPEG-PCL nanoparticles, GelMA hydrogel, hearing loss, gentamicin
format	article
author	Li X Wang Y Xu F Zhang F Xu Y Tang L Webster TJ
author_facet	Li X Wang Y Xu F Zhang F Xu Y Tang L Webster TJ
author_sort	Li X
title	Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
title_short	Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
title_full	Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
title_fullStr	Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
title_full_unstemmed	Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss
title_sort	artemisinin loaded mpeg-pcl nanoparticle based photosensitive gelatin methacrylate hydrogels for the treatment of gentamicin induced hearing loss
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/68a77a8f922a45daa4a79d363158397b
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Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss

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