Nanoparticle surface charges alter blood-brain barrier integrity and permeability
Nanoparticle surface charges alter blood-brain barrier integrity and permeability
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DOI：
10.1080/10611860400015936
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发表时间：
2004-10-01
影响因子：
4.5
通讯作者：
Allen, DD
中科院分区：
文献类型：
--
作者：
Lockman, PR;Koziara, JM;Allen, DD
目的：血脑屏障（BBB）是限制药物脑渗透的物理屏障和静电屏障。先前的工作已经证明纳米颗粒（NPs）克服了物理屏障，但关于NPs表面电荷对BBB功能的影响知之甚少。因此，这项工作评估：（1）中性，阴离子和阳离子带电的NPs对BBB的完整性和（2）NP brain permeability.Methods的影响：乳化蜡NPs制备从温暖的水包油微乳液前体使用中性，阴离子或阳离子表面活性剂，以提供相应的NP表面电荷。纳米颗粒的特征在于粒径和zeta电位。结果：中性NPs和低浓度的阴离子NPs对血脑屏障的完整性无影响，而高浓度的阴离子NPs和阳离子NPs则破坏血脑屏障。结论：（1）中性和低浓度的阴离子纳米粒可作为胶体药物载体进入脑组织，（2）阳离子纳米粒对血脑屏障有直接的毒性作用，（3）纳米粒的毒性和脑组织分布必须考虑其表面电荷。
Purpose : The blood-brain barrier (BBB) presents both a physical and electrostatic barrier to limit brain permeation of therapeutics. Previous work has demonstrated that nanoparticles (NPs) overcome the physical barrier, but there is little known regarding the effect of NP surface charge on BBB function. Therefore, this work evaluated: (1) effect of neutral, anionic and cationic charged NPs on BBB integrity and (2) NP brain permeability.Methods : Emulsifying wax NPs were prepared from warm oil-in-water microemulsion precursors using neutral, anionic or cationic surfactants to provide the corresponding NP surface charge. NPs were characterized by particle size and zeta potential. BBB integrity and NP brain permeability were evaluated by in situ rat brain perfusion.Results : Neutral NPs and low concentrations of anionic NPs were found to have no effect on BBB integrity, whereas, high concentrations of anionic NPs and cationic NPs disrupted the BBB. The brain uptake rates of anionic NPs at lower concentrations were superior to neutral or cationic formulations at the same concentrations.Conclusions : (1) Neutral NPs and low concentration anionic NPs can be utilized as colloidal drug carriers to brain, (2) cationic NPs have an immediate toxic effect at the BBB and (3) NP surface charges must be considered for toxicity and brain distribution profiles.