Enhanced neuroprotective activity of ophthalmic delivered nerve growth factor conjugated with cell penetrating peptide against optic nerve injury

Abstract

Aims: Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies.

Results: We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy.

Conclusions: This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury.

Keywords:

• Drug delivery
• recombinant human nerve growth factor
• cell penetrating peptide
• ophthalmology
• neuroprotection

Acknowledgements

The authors are grateful to the study team that contributed to the conduct of rhNGF and L-PenetraMax. We would also like to thank Dr. Jialei Yang (China National Clinical Research Center for Neurological Diseases)’s guidance and suggestions.

Ethical approval

The conduct of this study was in accordance with the guidelines of the Ethics Committee for the Institute of Experimental Animals. Prior to study initiation, the protocol was approved by the relevant Institutional Review Board or independent Ethics Committee at each centre.

Author contributions

All authors participated in the conceptualisation, data collection, analysis, interpretation, writing and critical review of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.