快速响应温敏水凝胶研究进展

温敏水凝胶是一类具有广泛应用前景的高分子材料,但是由于传统方法合成的水凝胶响应速率较慢因而限制了其应用,因此近年来围绕提高传统水凝胶的响应速率做了大量研究工作。本文从几个方面综述了近年来快速响应的温敏水凝胶的研究进展,并对有关现象进行了解释和说明。     

温敏性抗菌水凝胶的制备与控释技术研究进展

温敏水凝胶是一类通过感知温度变化使自身发生相变的智能型聚合物凝胶,通过负载抗菌剂或抗菌性单体制备抗菌水凝胶是近年来药物控制释放、组织工程以及生物免疫等领域关注的热点。本文概述了负载抗菌剂型温敏性抗菌水凝胶的物理交联和化学交联制备技术的研究概况,着重阐述了温敏性抗菌水凝胶的孔径调控、制备材料调控、载药模式调控等技术的研究进展,并对温敏性抗菌水凝胶的控释技术应用前景,特别是在生物质材料领域的应用前景进行了展望。     

温敏性水凝胶在抗菌领域应用的研究进展

智能水凝胶是一种能在水中溶胀而不溶于水的高分子聚合物,且能对外界刺激而作出应答的一类凝胶体系。温敏水凝胶是智能水凝胶的一种,它能根据环境温度的变化而产生体积相转变现象,与抗菌剂复合可使其具有抗菌活性。温敏水凝胶可以根据环境温度的变化间断式地释放抗菌剂,提高抗菌剂的效用时间,可应用于生物、医药、纺织等领域。本文介绍了温敏水凝胶的温敏机理,重点综述了近年来与抗菌剂相结合的丙烯酰胺、泊洛沙姆、壳聚糖及聚乙二醇-b-聚酯类共聚物等温敏性复合水凝胶在抗菌应用方面的研究进展,并探讨了近年来抗菌复合水凝胶研究存在的问题及未来的研究方向。     

水凝胶在人工眼角膜上的研究进展

理想的人工角膜植入材料要求物理化学性质稳定、生物相容性好、透光性高以及透气性好等,同时还应具有一定的折射能力,使得植入后能够达到矫正视力的目的。水凝胶因良好的生物相容性,及其对水溶性代谢产物如葡萄糖、营养物质、氧气等高的透过性,在眼科材料领域得到了非常广泛的应用。本文主要介绍了水凝胶材料在人工角膜上的研究进展,包括天然高分子水凝胶、合成高分子水凝胶、IPN互穿网络水凝胶以及高折射率有机-无机复合水凝胶。     

载药型硅基水凝胶角膜接触镜的研究进展

载药型角膜接触镜可以有效延长药物释放时间,提高药物的生物利用度,是一种较为理想的眼部给药方式。目前,在视力矫正领域,硅基水凝胶角膜接触镜因其具有高透氧和较低含水率的优点,已逐渐替代传统水凝胶角膜接触镜,被广泛使用,在眼科治疗及预防领域具有广阔的应用前景。本综述重点总结了近几年载药型硅基水凝胶角膜接触镜的研究进展,根据不同的载药方式对硅基水凝胶的基底结构、药物种类、药物释放机理等方面进行了详细分析,并对其发展前景进行展望。     

基于温敏水凝胶的可调胶体晶体制备

基于单分散胶体粒子悬浊液在温敏水凝胶表面可以形成湿润型胶体晶体的现象, 利用温敏水凝胶对水的控释作用制备了温度敏感的可调制胶体晶体. 在室温下利用提拉法在温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm)表面制备湿润型胶体晶体膜. 由于胶体粒子的有序排列, 胶体晶体显示出一个尖锐的反射峰. 当温度上升到34 ℃以上时, 由于PNIPAAm水凝胶中的水被释放, 导致胶体晶体中粒子浓度降低, 粒子间距增加; 反射峰发生红移. 这些特性可以通过温度变化进行调制.     

聚乙烯醇和丙烯酸-β-羟乙酯水凝胶的摩擦学特性

合成水凝胶是由水溶性单体聚合得到的轻度交联的高分子柔顺链网络 .高分子交联网络与水之间的相互作用决定着水凝胶的物理化学性质[1,2 ] .水凝胶常应用于生物医学材料和生物传感器等方面 .如接触眼镜的材料就常用甲基丙烯酸 -β-羟乙酯和聚乙烯醇 (PVA)为主要成分的水凝胶 ,所以对其摩擦性质的研究会丰富对生物医用材料的认识 .关于水凝胶的摩擦性质的研究 ,除 Osada等[3] 研究了聚乙烯醇及一些天然水凝胶在几牛顿到几十牛顿的负载下的摩擦行为外 ,尚少报道 .PVA水凝胶的结晶度对其性能影响甚大 ,但他们没有涉及结晶度与 PVA水凝胶的摩…     

载银离子PLGA-PEG-PLGA温度敏感水凝胶的制备及体外抗菌性能

利用聚乙二醇(PEG 1000)引发乙交酯和 D,L-丙交酯开环共聚合, 制备了聚丙交酯乙交酯(PLGA)三嵌段共聚物(PLGA-PEG-PLGA)温敏水凝胶材料; 利用核磁共振氢谱( ¹H NMR)确定了产物的结构及组成. 通过还原硝酸银的方法制备银纳米粒子(AgNPs), 并将其与PLGA-PEG-PLGA三嵌段共聚物水凝胶混合, 制得新型AgNPs/PLGA-PEG-PLGA复合水凝胶; 对该复合水凝胶的相关性能进行了表征. AgNPs/PLGA-PEG-PLGA复合水凝胶仍然具有温敏性能, 随着温度升高可发生溶胶-凝胶的相转变; 还可以持续释放银纳米粒子, 从而发挥抗菌性能. 体外细胞实验结果表明, AgNPs/PLGA-PEG-PLGA复合水凝胶具有良好的生物相容性, 未见明显细胞毒性, 是具有应用前景的新型复合水凝胶.     

天然五环三萜有机功能分子

天然五环三萜在自然界中广泛存在,由六个异戊二烯单元组成,可以从动植物中分离获取。因具有手性刚性骨架、多反应位点、独特组装性能、良好生物相容性及药理活性,其在超分子化学、智能材料、界面化学、药物传输等领域有着不可忽视的潜力。本文基于课题组近年来在天然五环三萜有机功能分子方面的工作,概述了含甘草次酸和甘草酸骨架的功能小分子和高分子的设计、合成及其在水凝胶、有机凝胶、有机-无机复合凝胶、手性材料、温敏和自愈合材料、农用Pickering乳液、准聚轮烷等方面的应用。     

温敏性PNIPAAm水凝胶对布洛芬的控制释放

采用自由基聚合法在水溶液中制备了温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm),以非水溶性药物布洛芬(IBU)为模型药物分子,研究了该水凝胶的温敏性能及与药物IBU的相互作用,考察了不同温度下(25 ℃和37 ℃)IBU在磷酸盐缓冲溶液(PBS,pH=7.4)中的释放行为.研究结果表明:该水凝胶的最低临界溶解温度(L...     

Recent developments of temperature-responsive polymers for ophthalmic applications

Blindness is one of the most feared disabilities. From cataracts and glaucoma to age-related macular degeneration and retinal vascular diseases, ocular diseases have adverse impacts on patients and pose a huge burden to the healthcare system. The World Health Organization estimates that out of 2.2 billion people with visual impairment, almost half of the cases can be prevented or has yet to be addressed. This presents an urgent clinical and societal need to be met. Temperature-sensitive hydrogels are one of the most biocompatible materials, which can be applied into the eye. By exploiting physiological temperature as a stimulus for in situ gel formation, control of the mechanical properties, rate of drug release, and biomechanical interactions can be tuned. They are very versatile and have immense potential in ocular applications by acting as vitreous substitutes in retinal surgery or topical eye drops and lenses for ocular discomfort and inflammation. In this article, we provide a review of the recent developments in temperature-responsive polymers in ophthalmic therapy in the past 5 years including retinal detachment, retinal vascular diseases, dry eyes, cataracts, age-related macular degeneration, and glaucoma.     

Soft Contact Lenses as Drug Delivery Systems: A Review

This review describes the role of contact lenses as an innovative drug delivery system in treating eye diseases. Current ophthalmic drug delivery systems are inadequate, particularly eye drops, which allow about 95% of the active substance to be lost through tear drainage. According to the literature, many interdisciplinary studies have been carried out on the ability of contact lenses to increase the penetration of topical therapeutic agents. Contact lenses limit drug loss by releasing the medicine into two layers of tears on either side of the contact lens, eventually extending the time of contact with the ocular surface. Thanks to weighted soft contact lenses, a continuous release of the drug over an extended period is possible. This article reviewed the various techniques to deliver medications through contact lenses, examining their advantages and disadvantages. In addition, the potential of drug delivery systems based on contact lenses has been extensively studied.     

硅基纳米探针用于眼部疾病的成像检测与治疗

快速精准的诊断和高效的治疗对于减轻眼部疾病造成的危害至关重要. 在过去的几十年里, 由于具有尺寸小、 比表面积大、 表面易修饰及独特的光/电子/机械性能等优点, 纳米材料已被用于构建不同种类的高性能纳米探针. 其中, 基于其良好的生物相容性, 科学家们已经将硅纳米材料设计为可用于不同眼部疾病诊断与治疗的功能化纳米探针. 本综述主要概述了将硅基纳米探针用于检测和治疗不同眼部疾病(如角膜疾病、 视网膜疾病、 青光眼等)的近期研究进展. 首先, 重点介绍了硅基纳米探针的设计制备及在角膜新生血管、 细菌性角膜炎等角膜疾病的成像检测与治疗中的应用; 然后, 介绍了用于成像检测和治疗视网膜疾病(如色素性视网膜炎和视网膜新生血管)的硅基持续性给药系统的研究成果; 随后, 概述了多功能硅基纳米载药系统的构建及在青光眼治疗领域的应用研究进展; 最后, 简要讨论了将硅基纳米探针用于眼部疾病诊治面临的挑战并对未来的发展前景进行了展望.     

Phase I and phase II ocular metabolic activities and the role of metabolism in ophthalmic prodrug and codrug design and delivery

While the mammalian eye is seldom considered an organ of drug metabolism, the capacity for biotransformation is present. Compared to the liver, the metabolic capabilities of the eye are minuscule; however, phase I and phase II metabolic activities have been detected in various ocular structures. The careful consideration of ocular tissue metabolic processes within the eye has important implications for controlling the detoxification of therapeutic agents and for providing the potential for site-specific bio-activation of certain drug molecules, thus enabling significant improvements in drug efficacy and the minimization of side-effect from either local or systemic drug delivery to the eye. Knowledge of these processes is important to prodrug and codrug development and to researchers involved in the design, delivery and metabolism of ophthalmic drugs. This present article reviews the progress in ocular prodrug and codrug design and delivery in light of ocular metabolic activities.     

Pediatric ocular nanomedicines:Challenges and opportunities

Challenges and opportunities to development of ocular drug delivery systems and nanomedicines for pediatric patients are reviewed.     

Stimulus‐Responsive Hydrogel for Ophthalmic Drug Delivery

Blindness and vision impairment are major global health problems. Effective ophthalmic drug delivery poses a significant challenge because of protective physiological barriers and various biological clearance mechanisms that result in extremely low ocular bioavailability. Over the past several decades, several safe and effective ophthalmic drug delivery approaches have been promoted to combat these problems and to improve ocular bioavailability. Among these approaches, the stimulus‐responsive hydrogel for topical drug delivery has gained increasing attention because of its prolonged drug retention at the local site and enhanced ocular bioavailability. This review summarizes and presents recent advances and perspectives of a stimulus‐responsive hydrogel for ophthalmic drug delivery.     

A green chemistry approach towards synthesizing hydrogel for sustained ocular delivery of brinzolamide: In vitro and ex vivo evaluation

Brinzolamide is a carbonic anhydrase inhibitor used in the eye drop form for the treatment of glaucoma. It requires frequent dosing to attain therapeutic concentration. Therefore, this study aimed to prepare sustained ocular drug delivery of brinzolamide. The objective of the study was to prepare a hydrogel loaded with a nanostructured lipid carrier (NLC) of brinzolamide. The hydrogel was prepared by a green synthesis approach using genipin as a natural crosslinking agent and polymers such as carboxymethyl chitosan and poloxamer 407. The melt emulsification-ultra sonication method was used to prepare a nanostructured lipid carrier of brinzolamide, which was loaded into a hydrogel using a swelling and loading method. The NLC formulation has shown small particle sizes of 111.20 ?± ?2.15 ?nm, polydispersity index of 0.280 ?± ?0.005 and % entrapment efficiency of 82.16% ?± ?0.14%. The NLC-loaded hydrogels of brinzolamide formulations were studied for swelling properties and showed temperature and pH-responsive swelling behavior. The optimized hydrogel formulation has been studied for in vitro drug release and showed drug release for a longer duration (24 ?h) than marketed eye drops (8 ?h). In an ex vivo study, hydrogel formulations showed transcorneal permeability 4.54 times greater than marketed eye drops. The hydrogel formulation of brinzolamide produced by the green synthesis method has shown sustained-release properties with no sign of ocular irritation. Hence, the hydrogel of brinzolamide-loaded NLC would be the potential drug delivery approach in the near future for sustained ocular drug delivery in glaucoma management.     

Recombinant protein-based polymers for advanced drug delivery

Advances in recombinant techniques have led to the development of genetically engineered polymers with exquisite control over monomer sequence and polymer length. The ability to study how precise structures correlate with function has provided opportunities for the utility of these polymers in drug delivery. Chemically derived and developed methods of synthesis have yielded many useful polymers for drug delivery to-date, including those currently used in patients. However they have drawbacks, including limitations involved in statistical characterization of conventional polymer synthetic techniques. Encoding at the genetic level and production of such recombinant polymers in organisms allow for precise order and accuracy of amino acid residues and production of monodisperse polymers with specific function and physicochemical properties. Research into elastin-like, silk-like, and silk-elastinlike protein polymers for example has led to the development of delivery systems based on natural motifs of structural proteins to take advantage of their physicochemical properties. Additionally, protein based polymers on other natural motifs and de novo designs are starting to produce promising constructs for drug and gene delivery applications where precise control over structure promises correlation with function and guides the development of new and improved constructs. Clinical applications based on recombinant polymers for delivery of bioactive agents have not been realized at this point. However lessons learned from fundamental research with these polymers can be used to guide design of safe and effective systems for use in the clinic. This tutorial review summarizes progress made in the design and utility of recombinant polymers in drug and gene delivery and discusses challenges and future directions of such polymers for this purpose.     

A highly selective fluorescent probe for visualizing dry eye disease-associated viscosity variations

Dry eye disease (DED) is a multifactorial chronic inflammatory disease of the ocular surface with complex and unclear etiology. The development of reliable detection tools for the pathology of DED will benefit its treatment, but it is still lacking. In parallel, it has been discovered recently that viscosity changes are involved in inflammation processes. In this regard, we constructed a fluorescent probe V5 with an asymmetric donor-acceptor-donor (D-A-D) feature after rational structural modulation for viscosity detection during DED progression. The probe manifested a remarkable fluorescence enhancement (110 folds) in highly viscous conditions without interferences from polarity and reactive species. Specifically, no aggregation effect of the probe was found in glycerol. Moreover, viscosity increment in human corneal epithelial cells (HCECs) induced by hyperosmosis and inflammation was monitored, and ferroptosis in HCECs also led to the viscosity elevation. A reactive oxygen species (ROS)-dependent viscosity changes during DED progression is demonstrated. Finally, viscosity change in corneal epithelial cell layer from mice treated by scopolamine was also visualized for the first time. We anticipate this work can provide a new lens to the pathogenesis study and diagnosis of DED and other ophthalmic diseases using fluorescence methods.     

纳米金属有机骨架材料及其载药应用

金属有机骨架材料(MOFs)是指由含氮、氧等多齿有机配体与金属离子通过自组装形成的配位聚合物。由于金属有机骨架材料的大比表面积和高孔隙率等优点使其在药物负载领域有广泛应用。近年来,纳米金属有机骨架材料(NMOFs)因既具有MOFs的特点,又具有纳米材料独特的理化性能,使其兼具药物负载量高、目标靶向性好、表面易改性和生物相容性优良等特点,已成为一种优异的纳米级载药系统。本文介绍了NMOFs的常用制备方法,主要包括溶剂热法、反相微乳液法与超声波法,并对其优缺点进行了讨论;详细阐述了载药NMOFs的特性及其不同类型对于各类药物的负载能力;指出今后其主要的研究方向是改善生物相容性、实现更有效的表面功能化、扩展生物NMOFs及其负载药物的种类,使其应用到更多疾病的治疗上。