Mistry Alpesh, Stolnik Snjezana, Illum Lisbeth
†Advanced Drug Delivery and Tissue Engineering Division, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, U.K.
‡IDentity, 19 Cavendish Crescent North, The Park, Nottingham NG7 1BA, U.K.
Mol Pharm. 2015 Aug 3;12(8):2755-66. doi: 10.1021/acs.molpharmaceut.5b00088. Epub 2015 Jun 15.
The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was augmented by addition of chitosan in solution, this was not reflected in the bioelectrical parameters and the metabolic activity of the tissue. Regarding transport across the excised olfactory tissue, none of the nanoparticle systems tested, irrespective of particle size or surface modification, was transported across the epithelium to appear in measurable amounts in the receiver chamber.
将治疗相关剂量的药物直接从鼻腔递送至中枢神经系统以治疗神经疾病的能力取决于高效药物递送系统的可用性。已显示包裹在纳米颗粒中的药物的递送和/或治疗效果有所提高；然而，药物和/或纳米颗粒从鼻腔向大脑转运的控制因素尚不清楚。本研究评估了纳米颗粒与纳米颗粒特性相关的跨嗅觉上皮的潜在转运。使用非修饰或用聚山梨酯80（P80 - PS）或壳聚糖（C - PS）进行表面修饰的20、100和200 nm荧光羧化聚苯乙烯（PS）纳米颗粒模型系统，评估其跨安装在垂直Franz扩散池中切除的猪嗅觉上皮的转运情况。对扩散池供体室中纳米颗粒含量的评估，以及对拆卸组织的荧光显微镜检查显示，取决于表面性质和粒径，供体悬浮液中的纳米颗粒含量有所损失，并且它们与切除的组织相关联。在测试系统中，壳聚糖对PS纳米颗粒的表面修饰导致最高的组织关联，相关的纳米颗粒主要位于黏液中，而聚山梨酯80修饰的纳米颗粒显示出一些渗透到上皮细胞层中。对切除的嗅觉上皮的生物电特性、代谢活性和组织学评估表明，在pH 6.0缓冲液中应用的C - PS纳米颗粒以尺寸依赖的方式对上皮细胞层产生损伤作用，相对于100和200 nm的纳米颗粒，20 nm的细颗粒导致大量组织损伤。尽管组织学显示嗅觉组织受到溶液中添加壳聚糖增强的柠檬酸盐缓冲液应用的影响，但这并未反映在组织的生物电参数和代谢活性中。关于跨切除的嗅觉组织的转运，无论粒径或表面修饰如何，所测试的纳米颗粒系统均未穿过上皮转运至接收室中出现可测量的量。
