Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain
Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain
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DOI：
10.3109/03639045.2015.1062897
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发表时间：
2015-12-02
影响因子：
3.4
通讯作者：
ElGamal, Safaa S.
中科院分区：
文献类型：
--
作者：
Hanafy, Amira S.;Farid, Ragwa M.;ElGamal, Safaa S.
目的：研究络合作为一种增强阳离子神经治疗药物氢溴酸加兰他明（GH）在阳离子壳聚糖纳米颗粒（CS-NPs）中的包裹性的方法，用于鼻内治疗阿尔茨海默病。选择生物可降解的CS-NPs是因为其生产成本低，制备简单。研究了络合对CS-NPs理化性质及大鼠脑内摄取的影响。方法：采用离子凝胶法制备安慰剂CS-NPs，筛选影响其理化性质的参数。利用红外光谱（FT-IR）对GH与壳聚糖形成的配合物进行了检测。采用离子凝胶法制备了GH/壳聚糖复合纳米颗粒（GH- cx - nps），并对其粒径、zeta电位、包封效率、体外释放度和在4℃和25℃条件下3个月的稳定性进行了表征。通过透射电镜观察安慰剂CS-NPs和GH-CX-NPs。制备罗丹明标记的GH-CX-NPs，经鼻给药雄性Wistar大鼠，用荧光显微镜和软件辅助图像处理技术检测给药1h后GH-CX-NPs在不同脑区的传递情况。结果：优化后的安慰剂CS-NPs和GH-CX-NPs的直径分别为182和190nm， zeta电位分别为+40.4和+31.6mV。GH包封率为23.34%，负载能力为9.86%。GH/壳聚糖的配位延长了GH的释放时间（72h后为58.07%6.67），提高了4℃时的药物泄漏和粒径稳定性，对优化后的安慰剂CS-NPs的理化性质影响不显著（p>0.05）。在嗅球、海马、眼窝额叶和顶叶皮层检测到罗丹明标记的GH-CX-NPs。结论：络合是一种很有前途的增强阳离子GH在CS-NPs中包裹的方法。对CS-NPs的理化性质影响不显著。GH-CX-NPs在鼻内给药后不久成功地递送到不同的大脑区域，这表明它们作为阿尔茨海默病管理的递送系统的潜力。
Objective: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined.Methods: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 degrees C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1h after administration using fluorescence microscopy and software-aided image processing.Results: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190nm, and a zeta potential of +40.4 and +31.6mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07%6.67 after 72h), improved formulation stability at 4 degrees C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p>0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices.Conclusion: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.