鼻腔给药的研究进展

鼻腔给药是一种极具潜力的药物转运系统。本文对影响鼻腔给药药物吸收的因素进行了介绍,并对鼻腔药物转运系统中所使用的药物吸收促进剂、生物粘附材料、研究方法等进行了综述。     

鼻腔给药系统药用辅料研究进展

介绍与分析国内外用于鼻腔给药系统(NDDS)的生物黏附剂、吸收促进剂及酶抑制药的种类、应用特点以及对鼻腔吸收的影响，综述用于鼻腔给药的药用辅料的研究进展，这些辅料对NDDS的成型、药物的吸收与疗效有重要影响。     

鼻腔给药的生物利用度研究进展

目前，鼻腔给药生物利用度的研究主要集中在吸收促进剂、药物性质、剂型和载体等因素的影响。虽然药物通过鼻腔吸收受诸多因素的影响，但由于鼻腔特殊的解剖生理结构，药物吸收迅速；且与其他给药途径相比，尤其对于多肽和蛋白类药物而言，鼻腔给药这种非侵入性给药方法更简单、安全并且节省费用，因此，有望成为未来全身给药的重要途径之一。本文综述了近年来药物经鼻腔给药的生物利用度的研究进展。     

鼻腔给药系统研究进展

近年来 ,通过鼻黏膜给药己被认为是一种药物能快速高效吸收的给药方式。鼻黏膜细胞上有很多微细绒毛 ,因此大大增加了药物吸收的有效面积 ,黏膜细胞下有着丰富的血管和淋巴管 ,药物通过黏膜吸收后可直接进入体循环。此外 ,鼻腔内酶的代谢作用远远小于胃肠道 ,因此 ,鼻腔给药系统正日益受到人们的重视 ,包括肽类和蛋白质类药物的研究。此外 ,药物从鼻嗅区吸收 ,为某些中枢神经系统疾病的治疗提供了一条有效的给药途径。另外 ,疫苗的鼻腔给药在疗效及患者接受性上同样是非常吸引人的。本文主要概述了设计和开发鼻腔给药制剂时需考虑的主要因素…     

鼻腔给药系统的鼻粘膜毒性及解决途径

就鼻腔给药系统可能导致的鼻粘膜毒性的评价方法、易产生毒性的制剂组分及解决毒性的方法进行简要的综述。     

鼻腔给药系统的研究进展

鼻腔给药系统（nasal drug delivery system，NDDS）是指在鼻腔内使用，经鼻粘膜吸收而发挥局部或全身治疗作用的制剂。鼻腔给药历史悠久，但过去大多用于治疗鼻炎、鼻塞等届部疾病，起局部消炎、收敛、杀菌等作用。近年来随着新辅粒和治疗新技术的应用，发挥全身治疗作用的鼻腔给药制剂酏研究越来越受到人们的广泛关注。     

吸收促进剂的作用机制及其在鼻腔给药中的研究进展

随着新的蛋白质及肽类治疗药物的开发,非侵入性给药途径-鼻腔给药日益受到关注。与口服给药和注射给药相比,鼻腔给药既可避免注射给药带来的生理和心理创伤,也可消除口服给药过程中肝脏的首过效应;且鼻腔黏膜下血管丰富,有助于药物的吸收,也更加便于患者的抢救和自救。然而,由于鼻黏膜屏障的存在,药物很难达到理想的治疗效果,因此需要加入鼻黏膜吸收促进剂来增强药物的吸收。该文主要探讨鼻黏膜吸收促进剂的作用机制及分类,并对FDA已上市鼻腔制剂中的吸收促进剂进行汇总,同时对新型黏膜吸收促进剂在鼻腔给药制剂中的应用进行阐述,以期为鼻腔给药制剂的开发提供依据。     

用于全身治疗的鼻腔给药系统

从药剂学角度对鼻的解剖生理及给药特点、影响药物在鼻腔中吸收的因素，特别就吸收促进剂和剂型因素与多肽和蛋白质类药物鼻腔给药的关系进行了综述。     

脑靶向性鼻腔给药的研究进展

鼻腔给药作为脑靶向给药的途径之一,可有效地使通过其他给药途径不易透过血脑屏障的药物绕过血脑屏障,靶向递送到脑部,为中枢神经系统疾病的治疗提供一种极有发展前景的给药途径.现从药物由鼻腔到脑的转运方式、影响因素、剂型、评价方法以及增强脑靶向性的方法等方面,对近年来鼻腔给药脑靶向性的研究进展进行综述.     

鼻腔给药系统研究进展

从鼻粘膜的生理特性、药物动力学、剂型、影响药物吸收及生物利用度的因素、对鼻粘膜的毒性、动物模型等方面综述鼻腔给药系统的研究进展情况.     

Mucoadhesive microspheres for nasal administration of cyclodextrins

The aim of this study was to examine the in vitro capacity of cyclodextrins to interfere on the β-amyloid fibril formation; then, mucoadhesive microspheres containing cyclodextrins were prepared and characterised as nasal delivery system for brain targeting. Eight batches of microspheres containing chitosan or alginate loaded with β-cyclodextrin or hydroxypropyl-β-cyclodextrin in two different cyclodextrin to polymer ratios were produced by spray drying. The results show that none of the tested CDs has direct cellular toxicity and they protect the cell viability from β-peptide. The microspheres prepared are characterised by small particle sizes, ability to absorb water and to delay the in vitro dissolution rate of the CDs; good ex vivo mucoadhesive properties of the formulations are assessed. The microsphere properties are influenced by the kind of polymer, of cyclodextrin and by cyclodextrin to polymer ratio used. In particular, the alginate formulation containing the higher cyclodextrin content shows the best performance.     

脑靶向鼻腔给药的研究进展

目的阐述鼻腔的生理特点和药物由鼻黏膜转运入脑的机制及其影响因素。方法依据近年来的29篇中外文文献,对药物的鼻腔脑靶向实验手段、离体在体模型、鼻黏膜的毒性等方面的研究进展进行阐述。结果鼻黏膜给药途径在脑内递药领域具有独特优势,其在脑部疾病治疗方面具有独到之处,值得进一步深入研究。结论药物的鼻腔脑靶向给药将受到越来越多的关注。     

胰岛素鼻腔喷雾剂的大鼠鼻纤毛毒性考察

目的：考察胰岛素鼻腔喷雾剂的鼻纤毛毒性。方法：扫描电镜观察鼻喷雾剂对大卤粘膜表面形态的影响。结果：大鼠给予胰岛素鼻喷雾剂后,扫描电镜观察,其鼻中卫粘膜的纤毛形态与给予生理盐水的对照组无显著差异。结论：上述胰岛素鼻喷雾剂无急性鼻粘膜纤毛毒性。     

Nicotine administration in rabbits using Habitrol nicotine patches and nicotine nasal spray

1. Several methods are used to provide predictable and effective nicotine to experimental animals in scientific studies. Due to the expense and technical challenges of these methods, we sought suitable alternatives. Consequently, the purpose of the present study was to develop a reliable experimental nicotine protocol in rabbits that included either Habitrol nicotine patches (Novartis Consumer Health Inc., Summit, NJ, USA) or nicotine nasal spray. 2. Administration of one of three doses of nicotine (2.5, 5, or 10 mg) was accomplished daily on 13 rabbits divided between either the patch or spray groups. Systemic nicotine and cotinine levels at 0 h, 15 min and 8 and 24 h were assayed. Data were analysed by a Fisher's protected least significant difference test at P = 0.05. 3. Rabbits treated with Habitrol patches exhibited consistent and predictable systemic nicotine levels. The nicotine nasal spray produced an immediate dose-dependent response with no measurable nicotine serum levels at 8 h. 4. For nicotine administration in rabbits, nicotine patches are easy to administer and provide a nicotine serum level between 5 and 25 ng/mL, which is consistent with the average daily level found in a patient who smokes cigarettes.     

中药白芷乳剂大鼠鼻腔给药的体内研究

目的：探讨白芷乳剂量腔给药的可行性。方法：以白芷主要有效成分欧前胡素和异欧前胡素为检测指标,探讨白芷乳剂大鼠鼻腔给药的药物动力学参数及脑组织中的含量。结果：欧前胡素和异欧前胡素鼻腔给药的tmax均为0．500h,Cmax分别为3．161,2．916μg/ml,AUC0p→∞分别为为20．205,28．117μg.h/ml,T1/2分别为4．779,6．301h,给药15min,即可透过血脑屏障,进入脑组织,4h时脑组织中含量分别为40．368,22．849μg/100mg。结论。白芷乳剂鼻腔给药具有一定的可行性。     

鼻腔给药新剂型研究进展

在鼻腔内使用，经鼻粘膜吸收而发挥全身治疗作用的制剂，称为鼻腔给药系统，鼻腔给药具有生物利用度高，吸收迅速，起效快，无损伤性，使用方便等特点，已成为制剂领域研究的热点之一，本文结合鼻腔的生理和给药的特点,综述了近年来鼻腔给药剂型的研究进展。     

眼镜蛇神经毒素粉末剂的鼻黏膜纤毛毒性考察

目的:考察浙江产眼镜蛇神经毒素鼻用粉末剂(神经毒素粉剂)的鼻黏膜纤毛毒性。方法:以在体蟾蜍上腭模型,观察神经毒素粉剂对鼻纤毛摆动的影响;运用组织病理学方法,在给于家兔神经毒素粉剂后1,3,5,7d时,取鼻中隔黏膜进行光学显微镜观察。结果:神经毒素粉剂抑制鼻纤毛摆动强度,但停止用药后8~9h纤毛摆动可完全恢复,且纤毛形态无明显改变;家兔给予神经毒素粉剂后1,3,5d,其鼻中隔黏膜与空白对照组差异无显著性。第7天,黏膜上皮松化,黏膜轻度充血,但基底膜完整。结论:神经毒素粉剂无急性不可逆性鼻黏膜纤毛毒性。     

Pharmacokinetics of Substrate Uptake and Distribution in Murine Brain After Nasal Instillation

No HeadingPurpose. This study was conducted to develop a physiologically relevant mathematical model for describing brain uptake and disposition of nasally administered substrates.Methods. [¹⁴C]-antipyrine, [¹⁴C]-diazepam, [³H]-sucrose, or [³H]-verapamil was administered nasally to CF-1 mice. P-glycoprotein (P-gp)-deficient mice also received [³H]-verapamil to probe the influence of P-gp on uptake/distribution. Mice were sacrificed at selected intervals, and 20 serial 300-m coronal brain sections were obtained to determine radioactivity. A series of compartmental pharmacokinetic models was developed and fit to concentration vs. time/distance data.Results. After nasal instillation, substrate concentration was highest in the olfactory bulb and decreased with distance. In the absence of transport-mediated flux, peak brain exposure occurred at 6 h. A catenary pharmacokinetic model with slice-specific brain-to-blood efflux rate constants and slice-to-slice diffusivity factors was capable of fitting the data. P-gp limited fractional absorption of [³H]-verapamil via efflux from the nasal cavity and olfactory epithelium. P-gp also increased the rate constants associated with [³H]-verapamil efflux 1.5- to 190-fold, depending on brain region. P-gp limited [³H]-verapamil uptake from the nasal cavity into brain and facilitated removal of [³H]-verapamil from brain during rostral-to-caudal distribution.Conclusions. Taken together, the data and associated modeling provide a comprehensive assessment of the influence of P-gp on brain uptake and disposition of nasally administered substrates.     

Plasma beta-endorphin,ACTH and cortisol secretion in man after nasal spray administration of calcitonin

Summary Beta-endorphin, ACTH and cortisol secretion were measured in twelve healthy adult males after nasal spray administration 200 IU salmon calcitonin.A significant increase in plasma beta-endorphin, from 19.2 ng/l under basal conditions to a peak of 27.1 ng/l at 30 min was recorded. Plasma ACTH and cortisol were not affected. In individual subjects the beta-endorphin level was increased in eight of the twelve, ACTH rose in three and cortisol did not change in any of them. The data indicate that calcitonin induced a beta-endorphin increase independent of enhanced corticotrophin-cortisol release.