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植物甘油三酯脂质基结晶纳米粒增强神经生长因子在耳蜗中的生物利用度。

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

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.

School of Pharmacy, Harbin Medical University, Harbin, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Nov 3;10:6879-89. doi: 10.2147/IJN.S82944. eCollection 2015.

DOI:10.2147/IJN.S82944
PMID:26604754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4639561/
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.

摘要

目的

将外源性神经生长因子（NGF）补充到失聪动物的耳蜗中，可以挽救螺旋神经节细胞免于退化。然而，安全有效地将治疗蛋白（如 NGF）递送到螺旋神经节细胞仍然是最大的挑战之一。本研究提出了一种自组装立方脂质基结晶纳米颗粒的方法，通过圆窗膜途径提高生物活性 NGF 的内耳生物利用度。

方法

基于植物三醇，通过液体前体稀释法开发了一种新型纳米载体包封的 NGF，其中 Pluronic（®）F127 和丙二醇分别作为表面活性剂和增溶剂。在液体脂质前体稀释时，轻微带负电荷的单分散亚微米颗粒会自发形成。

结果

使用载有 NGF 的储液器孵育嗜铬细胞瘤细胞来评估包封 NGF 的生物活性，结果诱导出明显的神经元突起，与游离 NGF 处理对照组相似。与游离药物相比，给予植物三醇脂质基结晶纳米颗粒后，内耳生物利用度增加了 3.28 倍，这有助于增强圆窗膜的药物渗透性。

结论

本文提供的数据表明，脂质基结晶纳米颗粒具有改善佩戴人工耳蜗患者疗效的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/10619ab34776/ijn-10-6879Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/f0ffe9499211/ijn-10-6879Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/cd2136c4893e/ijn-10-6879Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/4c8cc1d4b4a5/ijn-10-6879Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/1a2d35053f00/ijn-10-6879Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/178600be0322/ijn-10-6879Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/c7ecaf8c2f54/ijn-10-6879Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/10619ab34776/ijn-10-6879Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/f0ffe9499211/ijn-10-6879Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/cd2136c4893e/ijn-10-6879Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/4c8cc1d4b4a5/ijn-10-6879Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/1a2d35053f00/ijn-10-6879Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/178600be0322/ijn-10-6879Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/c7ecaf8c2f54/ijn-10-6879Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/4639561/10619ab34776/ijn-10-6879Fig7.jpg

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