角膜接触镜载药在青光眼药物治疗中的应用

角膜接触镜可通过多种方式(如浸泡法、维生素E修饰法、聚合物胶体纳米粒子载药法等)载一种以上药物形成眼部缓释系统,减少药物不良反应并增加其生物利用度。不同载药方式存在其局限性而限制其临床应用及产业化生产。浸泡法载药缓释系统药物突释明显,难以长时间达到有效的治疗水平;维生素E修饰法及聚合物薄膜载药法可更加有效延缓药物的释放,但可改变接触镜本身物理特性;聚合物胶体纳米粒子载药法可影响药物稳定性并造成大量药物浪费;环糊精及其衍生物可用于疏水性药物的缓释,也可影响接触镜本身物理特性;分子印迹法及超临界流体技术载药制作相对复杂,药物缓释效果影响因素多,难达产业化。(国际眼科纵览,2020,44:402-407)     

可溶性聚合物微针在眼部疾病药物递送中的应用研究进展

由于眼球特殊解剖结构和生理屏障的限制, 眼部疾病的药物递送极具挑战。眼部药物的传统给药方式普遍存在药物生物利用度低、缺乏组织靶向性等不足, 需多次给药以达到理想的药物治疗浓度。由于具备安全、微创、高效等特点, 微针近年来已被广泛应用于眼部药物递送的研究。而可溶性聚合物微针作为微针中的一大类, 因其相较于其他类型微针的独特优势已成为眼部给药领域研究热点。基于此, 本文对可溶性聚合物微针在眼部疾病药物递送中的应用研究进展进行总结和展望。     

纳米材料药物传输载体在治疗眼病中的应用

由于眼表面和眼内结构的解剖、生理屏障作用,常规眼部制剂一般无法到达特定位置发挥作用.纳米材料由于尺寸小、易制备、可降解、靶向性强以及对生物组织刺激性小等特点,不同类型的纳米材料在运载不同化学特性药物方面优势明显.目前,纳米材料作为药物传输载体在眼部给药方面应用越来越多,并被用于各种类型眼部疾病的治疗,显示出良好的应用前景.本文就纳米材料作为药物传输载体在眼科疾病治疗方面的应用作一综述.     

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。     

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。     

纳米控释系统在眼科给药方面应用的研究进展

纳米材料在眼部给药方面的应用主要集中在纳米控释系统,由于纳米材料的特有属性,使用纳米材料运载治疗眼部疾病的药物与传统给药方式相比具有很大的优越性,主要表现在药物的纳米制剂具有更高的生物利用率和更低的副作用。因此纳米控释系统在眼科具有良好的应用前景。目前,已经有多种不同类型的纳米控释系统被用于提高眼部给药效率的研究,包括纳米胶束、纳米颗粒、纳米混悬剂、脂质体和树突状分子等。本文就纳米控释系统在眼科给药方面应用的研究进展作一综述。     

纳米粒制剂在眼部用药的研究及展望

药物在眼部的传输对治疗有重要的影响.眼部存在多种生理屏障阻挡药物在眼内的转运.近年来,随着材料学和制药技术的飞速发展,眼部用药方式也有了新的进展.大量的药效学研究证明:采用纳米粒(nanoparticles,NP)作为肽类和蛋白质类药物的载体,能有效保护药物在短期内不会失活,并能实现缓释、控释和靶向给药,显著提高生物利用度,降低毒副反应.缓释、控释药物的研发有助于选择更为方便、有效的给药途径,尤其对眼后段用药意义重大.此文阐述眼部药物代谢动力学的必要因素及纳米粒在未来眼部药物制剂中的应用及发展前景.     

新型纳米材料在干眼中的应用进展

局部点药是眼部用药最常见的方式,但一般药物通过角膜困难,药物生物利用度低.纳米载体药物于80年代开始用于眼部,脂质体和类脂质囊泡(niosomes)与眼表的黏蛋白相互作用,延长药物在眼表的停留时间.纳米乳剂(nanoemulsion)的表面活性剂可以松解角膜上皮细胞紧密连接,形成转运开口,抑制细胞表面糖蛋白酶P(gly...     

本期导读

本期报道的重点内容是眼科临床用药研究。临床医师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,眼部给药系统的研究也快速发展。本期约请陈祖基撰写的“专家述评”《重视眼部给药系统的研究》一文,分析了眼部给药系统的研究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。FK506滴眼给药途径对高危角膜移植术后内皮层排斥反应的长期效果并不十分理想,提高FK506眼内药物浓度与确定最佳眼内…     

眼用药物缓释载体的研究进展

由于眼部的生理结构复杂和诸多屏障的存在,许多药物在眼科的临床应用受到限制.为了使药物在眼部更好地发挥药效,新型给药方法和技术的探索成为研究热点.近年出现的眼科药物缓释系统包括:(1)药胶粒系统如脂质体、微乳等;(2)微粒系统如微球、纳米粒、固体脂质纳米粒和纳米结构脂质载体等;(3)凝胶系统包括生物黏附性凝胶、原位凝胶等;(4)眼部植入系统包括插入剂和眼内植入剂等.     

基于分子印迹技术的载药角膜接触镜研究进展

分子印迹角膜接触镜（MI-CL）可有效延缓药物缓释和提高眼科给药效率。它不仅能显著降低患者因滴药带来的不适感,还可反复负载相关药物,并负载大分子量药物,在临床中具有巨大的应用潜力。笔者就MI-CL的原理、发展、载药和缓释模式等做一综述,为今后新型角膜接触镜设计和临床用提供可参考的资料。     

Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery

Approximately 90% of all ophthalmic drug formulations are now applied as eyedrops. Although eyedrops are convenient and well accepted by patients, about 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage. A major fraction of the drug eventually enters the bloodstream and may cause side effects. To reduce drug loss and side effects, it is proposed to encapsulate the ophthalmic drug formulations in liposomes and to disperse the drug-laden liposomes in the lens material. Upon insertion into the eye, the liposome-laden lens will slowly release the drug into the pre-lens (the film between the air and the lens) and the post-lens (the film between the cornea and the lens) tear films and thus provide drug delivery for extended periods of time. This paper focuses on dispersing dimyristoyl phosphatidylcholine (DMPC) liposomes in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels, which are a common contact lens material. The results of this study show that the p-HEMA gels loaded with liposomes are transparent and that these gels release drugs for a period of about 8 days. Contact lenses made of particle-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading.     

Nanotechnology in retinal drug delivery

Retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the leading causes of blindness in adults over the age of 50 years in the US. While most of those conditions do not have a cure, currently available treatment options attempt to prevent further vision loss. For many ophthalmic drugs, an efficient delivery system to provide maximum therapeutic efficacy and promote patient compliance remains an unmet medical need. An exploration of literature via PubMed spanning from 2007 to 2017 was conducted to identify studies that have evaluated nanotechnology as platforms for delivering therapeutic agents to the posterior segment of the eye where the retina is located. Until now, four routes that have been utilized for retinal drug delivery are the intravitreal, periocular, subretinal, and systemic routes. Intravitreal injections are now widely used in clinical practice due to their ability to directly target the back of the eye but are highly invasive procedures that may cause several complications, particularly with repeated uses over a short timespan. Nanotechnology shows great promise to revolutionize retinal drug delivery, offering many advantages such as a targeted delivery system towards the specific site of the retina as well as sustained delivery of therapeutic agents. In this review, specific eye anatomy and constraints on ocular drug administration are illustrated. Further, we list and highlight several examples of nanosystems, such as hydrogels, liposomes, dendrimers, and micelles, used via different drug delivery routes to treat various retinal diseases.     

The effect of therapeutic soft contact lenses on antibiotic delivery to the cornea

The effects of high (71%) and low (38.6%) water content lenses on antibiotic delivery to the cornea were studied in rabbits by measuring corneal tobramycin concentrations 1, 2, 4 and 6 hours after topical application at intervals of 15 minutes. In the presence of the low water content lens corneal drug levels were higher than in control corneas for every time point assayed. This difference was only significant at 4 hours (P less than 0.05). In eyes wearing the high water content contact lens corneal drug concentration was also higher at every time point tested except one hour. The difference was significant only at 4 hours (P less than 0.01). The data suggest that in the normal, noninflammed eye, the presence of a therapeutic soft contact lens will not compromise aminoglycoside delivery to the cornea.     

生物可降解载药微球经巩膜向眼内给药的研究

由于眼部复杂的生理结构和诸多屏障,使得全身给药后药物到达眼后段的量有限,疗效甚微。眼局部药物使用方便,但药物难以传递到视网膜。玻璃体内给药侵袭性大,危险性高。经巩膜给药有诸多优势,如巩膜表面积大,且位置表浅、操作简单,也不引起眼内屏障的损害。但要求药物在巩膜表面有适当的浓度,这个浓度过高会导致大量药物进入全身系统,引起全身不良反应;如果药物在巩膜表面浓度太低,通过巩膜进入脉络膜和视网膜所需的药物浓度梯度就难以建立。所以绝大部分 药物溶液不适合经巩膜给药。为了满足巩膜表面合适药物浓度的要求,科研工作者尝试研发并使用生物材料药物微球或巩膜表面给药装置进行经巩膜给药。相比于巩膜表面给药装置,微球不需要手术植入,简单注射即可,使用较为方便。     

Ocular gelling microspheres: in vitro precorneal retention time and drug permeation through reconstituted corneal epithelium.

PURPOSE: The model drug norfloxacin (NOR) was encapsulated into trehalose (TRH) and hydroxyethylcellulose (NAT) microspheres to obtain a novel gelling ophthalmic delivery system for prolonged release on corneal tissue. METHODS: We assessed NOR release from microspheres, prepared by the emulsion-solvent evaporation method. A new in vitro tear turnover model, including inserts containing reconstituted human corneal epithelium (RHC), was designed to evaluate the TRH/NAT microspheres' precorneal retention time. Bioadhesive properties of TRH/NAT microspheres were validated by using drug-loaded microspheres prepared with gelatine (GLT) commonly used as reference material in adhesion studies. RESULTS: In vitro drug release showed a typical trend of swelling systems. Precorneal retention tests showed that TRH/NAT microspheres maintained fluorescence in tear fluid for 81.7 min, whereas TRH/GLT microspheres and water solution maintained fluorescence for 51.8 and 22.3 min, respectively. NOR released from microspheres permeated throughout RHC slower (J(s) = 23.08 microg/cm(2)h) than NOR from commercial eye drops (J(s) = 42.77 microg/cm(2)h) used as the control. CONCLUSIONS: Adequate drug concentrations in aqueous humor could be prolonged after the administration of TRH/NAT/NOR microspheres. Good bioadhesive properties of the system and slow drug release on corneal surface might increase ocular NOR bioavailability.     

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。     

Novel approaches for retinal drug delivery

Novel methods of ophthalmic drug delivery are being developed to facilitate treatment of a variety of eye diseases. Pharmaceuticals administered intravitreally are able to bypass the blood-ocular barrier to achieve constant therapeutic levels in the eye, while minimizing systemic side effects. Sustained-release intravitreal implants are being developed to enhance further the intravitreal route of administration. Liposomes, microscopic vesicles with a membrane-like lipid bilayer surrounding an aqueous compartment, are being developed to incorporate a wide variety of drug molecules, proteins, nucleotides, and even plasmids giving them great potential for use in ophthalmology. Biodegradable scleral plugs containing pharmaceuticals have the advantage of biodegradability and the ability to fit in a relatively small diameter of 1 mm. Conjugate drugs, which are covalently linked, decrease drug solubility, which increases their half-life and also limits the amount of active drug present at a given time. Viral vectors have been investigated in the delivery of genetic material to the posterior segment of the eye. Retrovirus, adenovirus, adenoma-associated virus, herpes virus, and lentivirus have been investigated for gene transfer to the retina. Finally, iontophoresis, a method of drug delivery typically involving the application of low electric currents to drive molecules across barriers, such as skin, is being explored for ophthalmic applications.     

Ophthalmic drug delivery through contact lenses

PURPOSE: Currently available ophthalmic drug delivery systems are inefficient and may lead to side effects. To increase efficiency and reduce side effects, the authors propose disposable particle-laden soft contact lenses for ophthalmic drug delivery. METHODS: The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles and to disperse these drug-laden particles in the lens material, such as poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The drug-laden p-HEMA hydrogels were synthesized by free radical solution polymerization of the monomers in presence of nanoparticles. The particle-laden hydrogels were characterized by light-transmission and electron microscopy studies. Release profiles of lidocaine, a model hydrophobic drug, were measured by UV-Vis spectrophotometry. RESULTS: Microemulsions of hexadecane in water stabilized with a silica shell around the particles produced transparent hydrogels. Contact lenses made with particle-laden hydrogels released therapeutic levels of drug for a few days. CONCLUSIONS: Particle-laden hydrogels are promising candidates for ophthalmic drug delivery. They are transparent and can release drugs for extended periods. The drug delivery rates can be controlled by varying the loading of nanoparticles in the gel.