Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

Abstract

Purpose

Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.

Methods

A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic^® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.

Results

Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane.

Conclusion

Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants.

Keywords:

• nerve growth factor
• lipid-based crystalline nanoparticles
• PC12 cells
• inner ear drug delivery
• bioavailability

Acknowledgments

This research was undertaken in part on the SAXS beamline at the Beijing synchrotron, Beijing, People’s Republic of China. We thank Dr Guang Mo and Dr Zhihong Li of the Beijing synchrotron for their assistance in the setup of the SAXS beamline and further data analysis. We thank Dr Xiaojun Huang and Dr Gang Ji for technical support in cryo-TEM sample preparation and data collection and gratefully acknowledge the use of the TEM facilities at the Center for Biological Imaging (CBI), Institute of Biophysics, and the Chinese Academy of Science. This study was financially supported by the National Natural Science Foundation of China (grant number 81102401) and the Program for Zhejiang Leading Team of S&T Innovation (2012R10044 _05).

Disclosure

The authors report no conflicts of interest in this work.