肺表面活性物质治疗呼吸窘迫综合征给药方式的研究进展

肺表面活性物质(pulmonary surfactant,PS)作为一种“救命药”已常规用于新生儿呼吸窘迫综合征的防治,但对急性肺损伤/急性呼吸窘迫综合征的治疗效果仍存在一定的争议.PS的给药方式作为影响其疗效的关键因素受到了医学界的广泛重视,现有的PS给药方法主要有气管导管滴入法、经纤维支气管镜滴入法和超声雾化吸入法,各有优缺点,而操作简便的、非侵袭性的、有效的给药方式是未来继续研究的方向.     

siRNA给药途径的研究进展

RNA干扰（RNAi）通过在生物体细胞内导入外源性或内源性的双链RNA,使同源性mRNA降解、抑制特定基因表达而治疗某些基因异常所致的疾病,近年来已成为研究热点之一。文章就小分子干扰RNA（siRNA）的病毒载体给药、非病毒载体给药途径及优缺点做一综述。     

靶向给药体系在骨转移瘤中的研究进展

骨骼是除肝脏和肺脏外恶性肿瘤最常见的转移部位.骨转移(bone metastasis)被认为是临床严重的并发症之一.有文献显示超过70％的各类癌症晚期患者会发生骨转移,骨转移会诱发骨痛、病理性骨折、脊髓压迫和高钙血症等,因其导致的死亡率和致残率分别为20％和45％.在保证治疗原发肿瘤的基础上,怎样最大限度的治疗骨转移瘤和诱发最小的副作用是目前医学界研究的热点.靶向给药体系(targeted drug delivery system)包括双磷酸盐类、四环素类、单克隆抗体、聚乙烯亚胺等,它能有效的抑制骨转移,旨在为治疗骨转移提供更有效的策略.     

经皮给药系统的研究进展

经皮给药系统作为一种非侵入式药物递送系统,与传统的注射、口服等给药方式相比具有许多优势,非常适用于需要频繁治疗或长期治疗的疾病.根据近年来经皮给药系统的研究进展,对经皮给药机制、影响药物经皮渗透的因素、促进药物经皮吸收的方法进行归纳和评述,并对经皮给药系统的未来发展趋势进行展望.     

鼻腔给药系统的研究进展

鼻腔给药系统是指在鼻腔给药后，经鼻黏膜吸收从而发挥局部或全身治疗或预防作用的一类制剂。随着新辅料和新技术的逐渐应用，鼻腔以其可避免胃肠道酶的破坏作用和肝脏的首过效应，药物吸收迅速、起效快，易于被患者接受和顺应性好等特点，现已被看作是疫苗、激素、多肽等许多药物的最佳给药途径。目前，已经有一些蛋白质、多肽类药物的鼻腔给药产品上市，     

经皮给药治疗小儿肺炎疗效观察

目的探讨经皮给药治疗小儿肺炎的疗效. 方法将临床确诊的小儿肺炎患儿198例,按单纯随机抽样法分二组,对照组102例,用抗菌素或加用病毒唑治疗;治疗组96例在常规抗炎治疗基础上加用中药经皮给药治疗. 结果中药经皮给药治疗小儿肺炎可明显缩短肺部罗音消失时间及肺炎症状消失时间,缩短住院天数和提高治愈率. 结论在常规抗炎治疗基础上加用中药经皮给药辅助治疗小儿肺炎,有效、安全、无明显毒副作用.     

舒芬太尼经鼻给药与静脉给药在纤维结肠镜检查中疗效对比

目的 探究经鼻与经静脉的不同舒芬太尼给药方式应用在纤维肠镜的检查期间的临床效果。方法 选取2016年7月~2017年7月我院收治的62例患者的临床资料,依据给药方式分为对照组与研究组,每组31例。对照组行舒芬太尼静脉给药,研究组行舒芬太尼鼻滴给药,分析两组生命指标与临床指标。结果 研究组的心率与MAP低于对照组,SpO2高于对照组,差异有统计学意义（P＜0.05）;研究组的临床指标相比对照组指标优,差异有统计学意义（P＜0.05）。结论 纤维肠镜在检查时经鼻使用舒芬太尼临床效果更好,患者生命体征稳定,药物对呼吸抑制功能弱,有临床推广价值。     

人鼻粘膜的微血管构筑

用新鲜胎儿和新鲜成人标本作墨汁灌注连续切片、冰冻切片碱性磷酸酶染色光镜观察和微血管铸型扫描电镜观察方法研究了人鼻粘膜的微血管构筑。鼻甲粘膜内微动脉吻合形成两级微动脉拱。微静脉吻合形成浅、深静脉丛、下鼻甲粘膜的深静脉丛是由短而卷曲的微静脉吻合而成的致密静脉丛。在中、下鼻甲粘膜内观察到动－静脉吻合。对粘膜内微血管构筑的机能意义进行了讨论。     

经皮给药电穿孔技术的新进展

经皮给药是药物三大给药方式之一，经皮给药的电穿孔技术是一种新的经皮给药技术。这种技术可以增强大分子药物的经皮渗透速率，具有许多潜在的优点，近年来倍受人们的重视。皮肤角质层是阻止的经皮渗透的主要屏障，在皮肤上施加高压脉冲，使角质层结构瞬间紊乱产生可的亲水性“电孔道”，以增加药物的经皮渗透速率。     

鼻粘膜相关淋巴组织的研究进展

鼠类鼻粘膜相关淋巴组织是人类的Waldeyer's环的对应组织，为鼻腔免疫后诱导产生抗原特异性免疫反应的部位。最近发现特别在上呼吸道和生殖道鼻免疫比胃肠道免疫更有效地诱导系统和多处粘膜局部的免疫反应，而引起广泛关注。本文综述鼻粘膜相关淋巴组织的结构与其它粘膜相关淋巴组织的异同及其在局部和系统免疫中的作用等。     

右美托咪定经鼻使用在麻醉中的研究进展

右美托咪定为美托咪定的活性右旋异构体,是一种高效、高选择性的α2肾上腺素能受体激动剂,具有良好的镇静、镇痛和抗交感作用.同时对呼吸无抑制,可作为围手术期麻醉合并用药.右美托咪定经鼻给药是临床常用的方式之一,鼻腔黏膜毛细血管丰富,吸收药物迅速.与静脉给药相比,经鼻给药无创简便、刺激性小,起效缓慢平稳、易于被患者接受,因而...     

The influence of inadvertent intranasal buserelin administration in early pregnancy

Buserelin was inadvertently administered during 13 early pregnancies in 12 women with long-standing infertility, who had started the GnRH-agonist for gonadotrophin desensitization prior to ovarian stimulation for IVF. Six women delivered a healthy child and one pregnancy continues uneventfully. Three patients aborted before the sixth week and three women with tubal disease had an ectopic pregnancy. Corpus luteum function was normal in 11 of the 13 pregnancies. Although no evidence of embryotoxic effects of buserelin was observed, barrier contraceptive methods should be advised during the first days of its administration.     

Changes in hemostatic parameters after intranasal administration of peptide Pro-Gly-Pro

Anticoagulant activity, total and nonenzymatic fibrinolytic activity, and tissue plasminogen activator activity increased, while platelet aggregation and activity of factor XIIIa in rat blood plasma decreased over 3 h after single intranasal administration of proline-containing peptide Pro-Gly-Pro. Hemostatic parameters in rats 24 h after single administration of this peptide did not differ from the control level observed in animals receiving 0.85% NaCl. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 10, pp. 369–371, October, 2007     

Repetitive intranasal administration of cholecystokinin potentiates its central nervous effects

Functional evidence exists for a nose-brain pathway for the neuropeptide cholecystokinin-8 (CCK-8S). The transport mechanism, however, remains still unclear. Previous studies indicate a saturable dose-response curve on the magnitude of the late positive complex of the auditory event-related potential (AERP) with increasing doses of intranasally administered CCK-8S. Thus, the present study served to bypass this saturation by repeated lower dose intranasal administrations of CCK-8S. It was expected that this repetitive administration results in a nonsaturable dose-response effect on AERPs. AERPs reflecting cortical stimulus processing were recorded while subjects performed on an auditory attention task (oddball paradigm) four times (in intervals of 30 min) each following a separate 10-microg intranasal administration of CCK-8S or placebo. Compared with placebo, the repetitive intranasal administration of CCK-8S linearly enhanced the late positive complex and its subcomponent slow wave. Blood plasma CCK-8S levels were not affected by intranasal CCK-8S. The results suggest that by using a repetitive intranasal administration of CCK-8S, a saturable mechanism for central nervous CCK-8S effects can be avoided.     

Effects of intranasal administration of epitalon on neuron activity in the rat neocortex

This report discusses the properties of the synthetic tetrapeptide epitalon (Ala-Glu-Asp-Gly), synthesized on the basis of an epiphyseal peptide extract. Intranasal administration of epitalon was selected as a noninvasive means of applying the agent to the CNS by bypassing the blood-brain barrier. The aim of the present work was to assess the characteristics of the action of epitalon on the frequency of spontaneous neuron activity in the cerebral cortex of white rats. Studies were performed using male Wistar rats anesthetized with urethane (1 g/kg). Extracellular activity of cortical neurons was recorded with a glass microelectrode of resistance 1–2 MΩ. Recording of spontaneous neuron discharges for 10–15 min was followed by intranasal administration of epitalon solution and recording of neuron activity to 30 min after doses of 30 ng per animal. Significant activation of neuron activity was seen several minutes after dosage, with an increase (by factors of 2–2.5) in discharge frequency. In some experiments, the effect of epitalon was multiphasic. The first peak of increased neuron discharge frequency at 5–7 min was followed by peaks at 11–12 and 17–18 min. The increase in discharge frequency occurred because of an increase in the discharge frequency of neurons which were already active and the recruitment of previously silent neurons. At least the first peak of increased neuron activity following exposure to epitalon was found to be associated with the direct action of the peptide on cortical cells. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 8, pp. 949–956, August, 2006.     

Needleless intranasal administration of HVJ-E containing allergen attenuates experimental allergic rhinitis

Allergic rhinitis (AR) is one of the most common chronic diseases. Although current medications are highly effective in controlling its symptoms, they do not reverse the allergen-specific hypersensitivities that underlie the disease. Immunoglobulin E is a key mediator of AR, and preventing its production is clinically important. In this study, we developed an efficient needleless intranasal protein delivery system using the hemagglutinating virus of Japan envelope vector (HVJ-E). Intranasal delivery of ovalbumin (OVA) once a week for 3 weeks using this system enhanced OVA-induced interferon-gamma production by murine splenocytes. This treatment also attenuated the OVA-induced release interleukin-4 (IL-4) and IL-5 from splenocytes and the production of plasma OVA-specific immunoglobulin E in OVA-sensitive AR model mice. Thus, allergen-containing HVJ-E may be useful for noninvasive treatment of AR.     

Delivery of interferon-beta to the monkey nervous system following intranasal administration

We determined the nervous system targeting of interferon-beta1b (IFN-beta1b), a 20 kDa protein used to treat the relapsing-remitting form of multiple sclerosis, following intranasal administration in anesthetized, adult cynomolgus monkeys. Five animals received an intranasal bolus of [(125)I]-labeled IFN-beta1b, applied bilaterally to the upper nasal passages. Serial blood samples were collected for 45 min, after which the animals were euthanized by transcardial perfusion-fixation. High resolution phosphor imaging of tissue sections and gamma counting of microdissected tissue were used to obtain the distribution and concentration profiles of [(125)I]-IFN-beta1b in central and peripheral tissues. Intranasal administration resulted in rapid, widespread targeting of nervous tissue. The olfactory bulbs and trigeminal nerve exhibited [(125)I]-IFN-beta1b levels significantly greater than in peripheral organs and at least one order of magnitude higher than any other nervous tissue area sampled. The basal ganglia exhibited highest [(125)I]-IFN-beta1b levels among CNS regions other than the olfactory bulbs. Preferential IFN-beta1b distribution to the primate basal ganglia is a new finding of possible clinical importance. Our study suggests both IFN-beta and IFN-alpha, which share the same receptor, may be bound with relatively high affinity in these structures, possibly offering new insight into a neurovegetative syndrome induced by IFN-alpha therapy and suspected to involve altered dopamine neurotransmission in the basal ganglia. Most importantly, our results suggest intranasally applied macromolecules may bypass the blood-brain barrier and rapidly enter the primate CNS along olfactory- and trigeminal-associated extracellular pathways, as shown previously in the rat. This is the first study to finely detail the central distribution of a labeled protein after intranasal administration in non-human primates.     

Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration

In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.     

Effect of intranasal administration of γ-aminobutyric acid on intraspecies aggression of male mice

Intranasal administration of γ-aminobutyric acid (GABA) modifies the behavior of male mice in the intraspecies aggression model. Low doses of GABA (0.5 mg/kg) considerably decrease the number of attacks for several days. Systemic administration of GABA in high doses (100 mg/kg) induces short-term changes in the aggressiveness of male mice. It is hypothesized that intranasally administered GABA enters the central nervous system without crossing the blood-brain barrier. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4 pp. 401–403, April, 1997