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Thermoresponsive-co-Biodegradable Linear–Dendritic Nanoparticles for Sustained Release of Nerve Growth Factor To Promote Neurite Outgrowth
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-01-10 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b01044
Young Shin Kim , Muhammad Gulfam 1 , Tao L. Lowe 1
Affiliation  

Thermoresponsive and biodegradable linear–dendritic nanoparticles containing poly(N-isopropylacrylamide), poly(l-lactic acid), and poly(l-lysine) dendrons were investigated for sustained release of nerve growth factor (NGF) in response to temperature change. The nanoparticles and their degradants were not cytotoxic to neuron-like PC12 cells for at least one month. The nanoparticles were preferentially taken up by PC12 cells 6–13-times more at temperatures above (37 °C) than below (25 °C) the lower critical solution temperature of the nanoparticles. NGF could be loaded into the nanoparticles in aqueous solution and slowly released from the nanoparticles for 12 and 33 days at 25 and 37 °C, respectively. The released NGF was biologically active by promoting neurite outgrowth of PC12 cells. This work demonstrates a new concept of using thermoresponsive and biodegradable linear–dendritic nanoparticles for thermally targeted and sustained release of NGF and other protein drugs for the treatment of Alzheimer’s disease and other neurological disorders.

中文翻译:

Thermoresponsive-共同-Biodegradable线性-树枝状纳米粒子神经生长因子的缓释,促进突起生长

温敏和生物可降解的线性-树枝状纳米颗粒包含聚(Ñ -isopropylacrylamide),聚(-乳酸)和聚(-赖氨酸树突被调查为响应温度变化的神经生长因子(NGF)的持续释放。纳米颗粒及其降解物对神经元样PC12细胞至少一个月没有细胞毒性。在高于(37°C)的温度下低于低于(25°C)的纳米颗粒的临界溶液温度,纳米颗粒优先被PC12细胞吸收6-13倍。NGF可以加载到水溶液中的纳米颗粒中,并分别在25和37°C下分别从纳米颗粒缓慢释放12天和33天。释放的NGF通过促进PC12细胞的神经突向外生长而具有生物学活性。
更新日期:2018-01-10
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