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

Abstract

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.

• Authors: Xiaohua Li, Yanchun Wang, Feilong Xu, Feng Zhang, Ying Xu, Lei Tang, Thomas J Webster
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 15 Pg. 4591-4606 ( 2020) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 32612358 (Publication Type: Journal Article)
• Copyright: © 2020 Li et al.

Chemical References

• Artemisinins
• Ethylene Glycols
• Gentamicins
• Hydrogels
• Methacrylates
• Polyesters
• methoxy poly(ethylene glycol-co-epsilon-caprolactone)
• poly(epsilon-caprolactone)-b-poly(ethylene glycol)
• Polyethylene Glycols
• Gelatin
• artemisinin

Topics

• Animals
• Artemisinins (administration & dosage, pharmacokinetics, pharmacology)
• Drug Delivery Systems
• Ethylene Glycols (chemistry)
• Gelatin
• Gentamicins (adverse effects)
• Guinea Pigs
• HeLa Cells
• Hearing Loss (chemically induced, drug therapy)
• Humans
• Hydrogels (administration & dosage, chemistry)
• Methacrylates (chemistry)
• Nanoparticles (chemistry)
• Particle Size
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)