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

Authors Bu M, Tang J, Wei Y, Sun Y, Wang X, Wu L, Liu H

Received 15 February 2015

Accepted for publication 3 June 2015

Published 3 November 2015 Volume 2015:10(1) Pages 6879—6889

DOI https://doi.org/10.2147/IJN.S82944

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang

Meng Bu,1,2 Jingling Tang,3 Yinghui Wei,4 Yanhui Sun,1 Xinyu Wang,1 Linhua Wu,2 Hongzhuo Liu1

1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmacy, the Second Affiliated Hospital, 3School of Pharmacy, Harbin Medical University, Harbin, People’s Republic of China; 4College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China


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

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