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

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 Univers...

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Autores principales: Bu M, Tang J, Wei Y, Sun Y, Wang X, Wu L, Liu H
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:01f67e984e664297b45a7ed8712686492021-12-02T07:37:00ZEnhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea1178-2013https://doaj.org/article/01f67e984e664297b45a7ed8712686492015-11-01T00:00:00Zhttps://www.dovepress.com/enhanced-bioavailability-of-nerve-growth-factor-with-phytantriol-lipid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Meng 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, bioavailabilityBu MTang JWei YSun YWang XWu LLiu HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6879-6889 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Bu M
Tang J
Wei Y
Sun Y
Wang X
Wu L
Liu H
Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
description 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
format article
author Bu M
Tang J
Wei Y
Sun Y
Wang X
Wu L
Liu H
author_facet Bu M
Tang J
Wei Y
Sun Y
Wang X
Wu L
Liu H
author_sort Bu M
title Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
title_short Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
title_full Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
title_fullStr Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
title_full_unstemmed Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
title_sort enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/01f67e984e664297b45a7ed871268649
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