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

Authors Li X, Wang Y, Xu F, Zhang F, Xu Y, Tang L, Webster TJ

Received 8 January 2020

Accepted for publication 2 June 2020

Published 25 June 2020 Volume 2020:15 Pages 4591—4606


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo

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, USA

Correspondence: Xiaohua Li; Thomas J Webster
Tel +86013837160836; Tel +1 617 373 6585

Objective: 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

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