眼用给药系统的研究进展

由于眼部生理结构复杂和诸多屏障的存在,许多药物对眼部疾病的治疗作用甚微。为了更好地使治疗药物进入眼内发挥疗效,眼部给药的途径也是药剂学研究的热点之一。本文就近年来凝胶系统、胶粒系统、微粒系统、植入剂等眼用给药途径的研究进展作一综述。     

眼科缓释新剂型——微粒体眼用给药系统

眼科缓释新剂型——微粒体眼用给药系统张俊杰徐岩综述陈祖基审校（河南省眼科研究所，郑州４５０００３）一、前言许多局部眼用制剂的生物利用度差，因而在治疗应用时受到了限制，尤其在治疗眼后部疾病时，药物在玻璃体内滞留时间短，为了达到玻璃体内的药物治疗水平，必...     

眼部控释给药系统的研究进展

由于眼组织特殊的生理生化环境和诸多生理屏障的存在,致使长期以来眼科临床对许多慢性眼病（如ＰＶＲ,巨细胞病毒性视网膜炎,青光眼术后纤维化等）的药物治疗疗效欠佳。为此,研制一种能够长期稳定释放药物,对眼组织无毒副作用,生物相容性高,疗效佳的眼部控释给药系统是近年来眼科学者和药剂学家普遍关注的新课题。本文就近年来眼部控释给药系统的研究进展作一综述。     

舒芬太尼在兔眼局部用药的急性毒性研究

目的：研究舒芬太尼对兔眼部用药的急性毒性反应,为其临床局部安全用药提供理论依据。

方法：将16只健康成年新西兰兔随机分成4组。1组为对照组,以空白溶剂作溶媒对照; 2,3,4组家兔左眼分别滴舒芬太尼注射液5μg(2滴,5min内)、7.5μg(3滴,10min内)、10μg(4滴,15min内),同时各组右眼以9g/L NaCl溶液作为自身对照,滴速相同。滴药后的7d后进行局部毒性研究。

结果：肉眼及裂隙灯观察：各组角膜无混浊、结膜无明显充血和水肿、无分泌物、虹膜正常,无产生暂时闭目现象。内皮照相：各组的角膜内皮细胞计数无统计学差异; 光镜观察：结膜、角膜、角巩缘、虹膜、睫状体、视网膜及视神经均未发现有病理形态学损伤。

结论：单次使用5～10μg舒芬太尼眼部给药进行镇静、镇痛在短期内是安全的。     

眼用抗血管内皮生长因子水凝胶药物缓释系统的研究进展

水凝胶具有优良的生物相容性及与玻璃体类似的光学和流变性,能比较容易地进行玻璃体注射,且具有药物缓释的特点,可以作为抗血管内皮生长因子(vascular endothelial growth factor ,VEGF)药物缓释系统载体应用于各种视网膜脉络膜疾病的治疗。近年来,已有多种类型的水凝胶载体在动物模型中研制成功,...     

脂质体在眼部给药系统中的研究进展

脂质体易与生物融合,具有很好的生物相容性,且无毒、无免疫原性。对脂质体在眼部给药系统中的应用进行综述,分别从脂质体在眼部局部给药、玻璃体内给药、结膜传递等角度分析了脂质体在眼部给药系统中的最新研究进展。     

眼前段药物缓释系统研究进展

目前眼前段药物缓释系统的研究主要有前体药物、佐剂、聚合物凝胶和胶体剂型等。前体药物和佐剂研究较早,应用较多;聚合物凝胶、胶体剂型等具有更好的药物缓释性、更高的生物利用度且患者舒适度较高,是现在眼部用药研究的热点。（国际眼科纵览,2015,  39: 297.302）     

壳聚糖在眼表给药系统及眼组织工程中的研究进展

壳聚糖是一种带正电荷的天然高分子聚合物,地球蕴藏量十分丰富,具有优良的生物学特性,现已成为生物医学领域中的研究热点,它在眼科领域的研究也日益深入.此文将结合壳聚糖的生物学特性,就其在眼表给药系统及眼组织工程中的研究进展作一综述.     

眼内缓释给药的研究现状

药物疗法是防治多种眼内增生性、感染性和变性疾病的重要措施之一，而眼内缓释给药系统是实现高效、低毒局部药物治疗的一种有效手段。近年来有关眼内缓释给药系统的研究包括脂质体、纳米粒、微粒体、植入体和巩膜塞等。离子电渗给药作为一种物理控释给药途径也受到关注。[眼科新进展2005；25（5）：464—466]     

The ocular tolerability of a new ophthalmic drug delivery system (NODS)

In an open label, two period cross-over study we compared the ocular tolerability of NODS vs. Isopto-Naturale^R eye drops. Thirty healthy volunteers were asked to rate the application system they were using for ocular discomfort, utilizing a visual analog scale in which 100=no ocular discomfort and 0=severe ocular discomfort. In addition each subject had to answer a questionaire and underwent a full ophthalmic control before, at day 7, at day 14 and at day 21 of the study. Each application form had to be applied to one eye only once a day for 7 days, followed by a washout period of 1 week. The type of application form was then changed and again had to be applied to one eye only for 7 consecutive days, followed by a final ophthalmic examination. The mean irritation score was recorded at day 7 and at day 21 of the study. Volunteers had no history of eye disease, no acute pathology of the eye, no contact lenses, no conditional foreign body of the cornea within the last four weeks prior to the study or within the study, no local therapy, no systemic therapy, no diabetes, no pregnancy. Informed consent was obtained. At day 1 one of the two application forms was given to each volunteer in a randomized order. 29 volunteers finished the protocol (16 male, 13 female); mean age: 26 years (range 20–32 years). The mean irritation score of NODS: 35 (2-81); the mean irritation score of Isopto-Naturale^R: 80.4 (45.5–99). The difference of mean irritation score (NODS vs. Isopto-Naturale^R): 46.7 (3.3–82.1) (p<0.01). The results of the study indicate that in healthy volunteers NODS are not as well tolerated as conventional eye drops when compared for ocular discomfort. However, the chance of applying drugs without preservatives and the possibility of increasing the rate of bioavailability from the new route (NODS) as well as the proportionally reduced risk to the patient of systemic side effects after NODS application of any type of drugs should be taken into consideration.     

眼内色素在眼部药物传递中的作用

眼内色素主要存在于葡萄膜（包括虹膜、睫状体、脉络膜）和视网膜色素上皮（RPE）层,它能与很多不同类型的药物结合,如抗生素、麻醉剂、β-受体阻滞剂、糖皮质激素和抗疟药等,结合的关键在于药物的酸碱度和脂溶性.通过研究药物在不同给药途径中的药代动力学和药效学,发现眼内色素与药物的结合在眼部药物传递中起重要的作用.它不仅可以提高药物在组织中的初始浓度,而且色素与大部分药物的结合是可逆的,使得药物可以从色素中缓慢释放而延长药物的作用时间,产生有利或不利的影响.由于不同的药物与色素的结合力不同,且在不同的物种和种族,甚至同一组织的不同区域中眼内色素的含量都有区别,使得药物与色素的结合存在个体差异,因此进一步研究不同药物与眼内色素结合的特点和量化关系,可以为科研和临床用药,特别是经巩膜给药的研究和药物递放系统的开发提供更多的科学依据和指导意义.     

纳米给药系统在眼科的应用

纳米颗粒是纳米尺寸范围内的胶体载药系统,具有靶向、控释和跨生物膜给药等特点,可有效提高药物在眼部的生物利用度。研究发现,纳米制剂眼表给药在青光眼、眼内炎症和感染等治疗方面有极大的应用潜力。     

Nanoparticles in the ocular drug delivery

Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases.     

重视眼部给药系统的研究

选择恰当的给药系统能明显增强药物疗效、延长作用时间及减少不良反应。近年来随着高分子化学的研究进展,眼部给药系统研究也快速发展。为了更加重视眼部给药系统的研究,笔者简述了眼部给药系统研究的进展和我国研究发展概况,并就开发我国自主知识产权的高分子聚合物材料,正确开展新型眼部给药系统的眼内药代动力学和眼毒理学研究进行了评述。     

Nanostructure-based platforms-current prospective in ophthalmic drug delivery

The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists.     

Bioavailability of vitamin B using a small-volume nebulizer ophthalmic drug delivery system

BACKGROUND: To determine the intraocular bioavailability of a novel embodiment for vitamin B(12) delivered to the ocular surface by a piezo-electric ultrasonic nebulizer. METHODS: The semisolid embodiment contained 0.02% (w/w) vitamin B(12) in 1 g of ointment, which was immiscible and insoluble in 5 mL sterilized warm water. To confirm in vitro functionality, nebulized mist particles of the embodiment were collected and analysed for vitamin B(12) content. The in vivo arm of the study was designed as randomization of 23 patients who were scheduled to undergo cataract surgery in hospital. Fourteen patients were treated with nebulized vitamin B(12), five patients had one drop of 0.02% vitamin B(12) instilled in the conjunctival cul de sac, and four control patients had no medication. Twelve hours after the vitamin was delivered, the patients underwent the cataract procedure and a sample of aqueous humour was collected from each. High performance liquid chromatography was used for detection of vitamin B(12) in all samples. RESULTS: The in vitro analysis of mist particles showed increasing concentrations of vitamin B(12). In the patient tests, analysis of the aqueous humour samples showed that none of the controls or those receiving eye drops had detectable vitamin B(12) in the aqueous humour. However, 4 of 14 in the nebulizer group had vitamin B(12) detected in the aqueous humour in the amount of 10(-7) mol. CONCLUSIONS: The small-volume nebulizer system might provide another method of ophthalmic drug delivery.     

外排转运蛋白在眼部给药中的研究动态

外排运转蛋白是一种广泛分布于人体全身组织器官的细胞膜转运蛋白,它可以将进入细胞内的外源性物质,包括药物等转运出细胞外,对细胞起到保护作用.近年研究表明,该蛋白亦分布于角膜、虹膜、睫状体、视网膜神经上皮和视网膜色素上皮(RPE)等眼部组织,每种转运蛋白都有其相对应的特异性底物及抑制剂.外排转运蛋白通过其对药物的外排转运功能影响不同给药途径中药物在眼内的利用和分布.深入研究外排运转蛋白药物的吸收和分布,清除时所起的作用,有助于进一步了解眼部给药的机制和设计给药方略,为临床眼部给药和给药途径的开发提供更多的科学依据.