刺激响应性聚合物胶束的研究概述

刺激响应性聚合物胶束是一种对内源性或外源性环境有响应的新型聚合物胶束,它随内源性或外源性环境的变化,表现出与众不同的物理化学性质。由于肿瘤组织和正常组织在物理化学性质以及对内源性或外源性环境变化的敏感性方面存在差异,因此化疗药物负载刺激响应聚合物胶束被认为是肿瘤治疗的很有前景的途径。概述了近年来刺激响应性聚合物胶束的研究进展。以期为刺激响应性聚合物胶束的应用提供参考。     

聚合物胶束的稳定性及影响因素

由两亲性大分子自行组装形成的聚合物胶束被广泛地应用于抗肿瘤药物的靶向输送,但是聚合物胶束纳米载药系统面临着困境,即胶束进入人体内后其稳定性大大减弱,导致药物的提前释放从而失去了靶向作用。因此阐明影响聚合物胶束稳定性因素是进一步设计和制备物理稳定的聚合物胶束药物输送载体的基础。本文从热力学和动力学角度概述聚合物胶束稳定性的影响因素,并进一步探讨了其作为重要的药物输送载体在人体血液循环系统中受到血液微环境等不利因素的影响。     

聚合物载体及胶束载药控释靶向研究进展

近年来,聚合物纳米载体受到各领域的广泛关注。其中,胶束因其自组装形成特殊的核壳结构,成为研究的热点。本文简单介绍了聚合物药物载体,总结了胶束在自组装载药、响应性控释和靶向性传递方面相关研究进展。     

环境响应性两亲嵌段共聚物的自组装及其药物控释研究进展

两亲嵌段共聚物形成的胶束、囊泡等典型的自组装体可作为纳米医药载体,用于药物的控释,其研究已成为当前胶化、医药和生物学科交叉领域的热点。尤其是聚乙二醇型两亲嵌段共聚物,不仅具有良好的生物相容性,而且通过适当的分子设计可形成对环境具有刺激响应的纳米载体。本文着重综述了这类两亲嵌段共聚物的自组装及其在药物控释方面的研究,总结了影响自组装的因素,并介绍了控释药物的机理。     

水溶性紫杉醇两亲性共聚物纳米胶束研究

聚乙二醇聚己内酯聚乙二醇采用三嵌段共聚物为载体包载紫杉醇形成纳米胶束,胶束具有明显的核壳结构,有效地改善了紫杉醇的水溶性。研究表明,采用蒸发溶剂法、透析法和熔融法制备的胶束对紫杉醇都呈现良好的包封效果,其中,以熔融法制得的胶束粒径最小,分布最窄。文中还考察了蒸发溶剂法实验条件对胶束的影响,发现低沸点有机溶剂有利于获得小粒径胶束,胶束平均粒径随着载药量的提高相应增大。体外释药的结果表明,载药量高的胶束释药率却相对较小。     

基于嵌段共聚物交联制备稳定纳米胶束的研究

两亲嵌段共聚物通过自组装形成纳米胶束,并通过对胶束结构的具体区域进行交联,能够将胶束结构固定下来,对纳米材料的制备及药物的运载、控制释放等带来极大的帮助。本文综述了Wooley,Armes,Liu等在壳交联及核交联方面所做的研究,从制备方法,到功能性胶束的开发以及应用领域的研究进展进行了具体的阐述,并进行了展望。     

聚合物胶束作为药物载体的应用

作为药物载体聚合物胶束具有其他纳米载体所不具有的优势,如良好的稳定性和靶向性等.本文综述了聚合物胶束的种类、自组装原理、制备方法、载药方法和释药机理.     

环境刺激响应型水凝胶及其在药物控释中的应用

环境刺激响应型水凝胶又称智能水凝胶,因为它能感应到外界环境因素的变化,并且发出响应,从而导致药物可在定点,定时、定量地释放,所以近年来受到普遍重视.该文综述了近年来响应水凝胶中温度敏感型、pH敏感型以及葡萄糖、电场、磁场、光等敏感型水凝胶及其在药物控释中的应用的最新进展,指出目前研究环境刺激响应型水凝胶存在的问题及今后...     

Pluronic嵌段共聚物胶束作为靶向药物载体

聚氧乙烯 聚氧丙烯 聚氧乙烯 (PEO PPO PEO)三嵌段共聚物 (商品名为Pluronics)在水溶液中能自发生成多分子聚集的胶束 ,这些胶束主要以疏水的PPO嵌段为内核 ,PEO嵌段环绕在外构成外壳 ,这种胶束可以有效地增溶油溶性药物。Pluronic嵌段共聚物无毒、无刺激、无免疫原性 ,胶束外壳的PEO嵌段能阻止血小板的聚集。胶束尺寸和病毒相仿 ,其大小适合在体内传输。初步尝试表明 ,胶束表面嵌上合适的抗体可以将增溶了模型药物的Pluronic胶束定向输送到动物脑部 ,从而提高了药效 ,降低了副作用。实验表明 ,Pluronic嵌段共聚物胶束可能成为将多种药物导向特定部位的有效载体。     

光敏感型嵌段聚合物胶束的研究进展

对聚合物结构中常见的光敏感性基团进行了介绍,并根据嵌段共聚物结构设计和光敏感基团的差异,将光敏感型嵌段聚合物胶束（BCPM）分为侧链变化型、主链断裂型、主链降解型和疏水交联型等几类,并对这几类BCPM的结构特征及其光刺激下结构的变化进行了对比分析,重点阐明了各类BCPM作为药物载体材料时对药物的光控包载或释放行为。光敏感型BCPM具有良好的结构可控性和刺激响应能力,通过结构的进一步优化和研究的不断深入将有望发展成为一类新型的药物靶向输送系统。     

Responsive polymeric nanoparticles for controlled drug delivery

Small‐molecule drugs often have limited solubility, display rapid clearance or poor selectivity that leads to undesired side‐effects. Although prodrug strategies can improve solubility and lower toxicity, activation ‘on demand’ as well as targeted transport of prodrugs remains a challenge in drug delivery. Responsive polymeric nanoparticles can help meet these challenges with the encapsulation or conjugation of drugs, allowing release at the target site upon triggering by an internal or external stimulus. The adaptable design of polymeric nanoparticles allows them to play a vital role in achieving a specific and desired response following application of a specific stimulus. Here, the most recent progress in responsive polymeric nanoparticles is reviewed with a focus on the chemical properties of the utilized polymers. © 2017 Society of Chemical Industry     

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

pH responsive hydrogels are ideal platforms for numerous therapeutic delivery applications, including oral delivery, as they are capable of overcoming the many barriers that must be considered when creating an effective drug delivery system. Understanding of the innate hydrogel network structure and its swelling behavior at environmentally relevant conditions is vital for designing hydrogel network capable of effective controlled drug release. Herein, we explored how to expand traditional techniques of swelling and pore characterization to gain better insight into the performance of anionic microparticles composed of the poly(methyl methacrylate-co-acrylic acid) with varying molar percentage of 10, 20, and 30 mol% of MMA, for controlled release of low-molecular-weight drugs. By evaluating these carrier systems at environmental conditions, we can observe changes in swelling and pore size of the anionic hydrogel networks as a function of MMA, which was then correlated with the release profiles of the small-molecular-weight drug sodium nitrate. With the correlation of the swelling behavior of the networks and the release profiles, we demonstrated how the expansion of swelling parameters at relevant pH values provides further incite for evaluating for the optimal blend for controlled release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48767.     

Stimuli-responsive hybrid microgels for controlled drug delivery: Sorafenib as a model drug

Microgels (MGs) are synthetic colloidal hydrogel particles made of three dimensional polymer networks. Their chemical composition is crucial for their use as intelligent drug release systems operated by temperature control. Herein, several MGs using N-isopropylacrylamide (Nipam)/N-isopropylmethacrylamide (Nipmam), chitosan and acrylic/methacrylic acid have been synthesized by free radical polymerization reactions (NC MGs) and the effects of surfactants and different reaction times on size and swelling properties have been investigated. MGs have been identified and characterized by dynamic light scattering and atomic force microscopy, and finally used to optimize the encapsulation protocol of the hydrophobic drug sorafenib. The drug delivery system here described has encapsulation efficiency of 40% and releases 10% of the entrapped drug over about 16 h after the temperature is raised above the volume phase transition temperature. Data suggest that MGs with optimized composition may act as properly instructed entities able to trap and release biomolecules following external stimuli.     

One dose or two? The use of polymers in drug delivery

Controlled‐release delivery systems are designed to prolong the release of drugs within the body. They consist of drug molecules encapsulated within biodegradable polymers which degrade safely into small, non‐toxic fragments, resulting in the release of the drug. Because different polymers have different degradation times, the system can be tailored to achieve the desired release rate and this can be very useful in treatments where daily dosing is required, such as epilepsy. Despite this obvious advantage, there are problems with this type of delivery, including an increased risk of overdosing. This article examines the pros and cons of controlled‐release drug‐delivery systems. Copyright © 2007 Society of Chemical Industry     

Preparation of polymer nanoparticles loaded with doxorubicin for controlled drug delivery

The preparation of polymer nanoparticles loaded with an active principle, commonly used in cancer treatment, is investigated here from the experimental point of view. The main novelty of this work stands in the use of continuous confined impinging jets mixers in combination with realistic materials, notably the biodegradable and biocompatible copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) together with two forms of the drug doxorubicin. To our knowledge this is the first attempt to use for such a system a device that can be operated continuously and can be easily scaled up. Nanoparticles are produced via solvent-displacement experimenting different solvents; the effect of the other operating parameters is also investigated. Nanoparticles are characterized in terms of their size distribution and surface properties; for a limited number of samples prepared with the optimized preparation protocol further characterization (in terms of drug loading, incorporation and release profiles) is also carried out. Collected results show that the overall approach is capable of producing nanoparticles with controlled particle size distribution, drug loading and good reproducibility and that on the contrary of what reported in the literature the presence of the active principle does play an important role.     

果胶-壳聚糖聚合物在药物释放系统中的应用进展

介绍了果胶-壳聚糖聚合物的研究情况,以及果胶-壳聚糖聚合物在口服药物释放系统中的应用研究,主要研究形态为水凝胶、复合膜、微粒、包衣和片剂,最后提出新的研究方向。     

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix^® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise^®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix^® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.     

Preparation,properties, and mathematical modeling of microparticle drug delivery systems based on biodegradable amphiphilic triblock copolymers

A series of biodegradable amphiphilic A‐B‐A type triblock copolymers P(BLA‐PEG‐BLA), composed of hydrophilic poly(ethylene glycol) (PEG) as a middle block component (B) and hydrophobic poly(β‐benzyl‐L ‐aspartate) as outer polypeptide block components (A), were synthesized by copolymerization of β‐benzyl‐L ‐aspartate N‐carboxy anhydride (BLA‐NCA) and the diaminated PEG with the primary amino groups capped at both ends. These P(BLA‐PEG‐BLA) copolymers were characterized by ¹H‐NMR, DSC, and GPC. The triblock copolymers were used to prepare three kinds of drug delivery systems including Norfloxacin (INN)‐incorporated P(BLA‐PEG‐BLA) microparticles and tablets. The morphologies of the microparticles were characterized by SEM. The in vitro release properties of the microparticles and tablets in PBS were also evaluated. A mathematical model, which incorporates a linear first‐order dissolution term and the transient Fickian diffusion equation, was developed to account for the kinetics of drug release from the INN‐incorporated P(BLA‐PEG‐BLA) microparticles. The results indicated that the overall release process was well controlled by both drug dissolution and diffusion. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 3869–3873, 2004     

Drug transport in stimuli responsive acrylic and methacrylic interpenetrating polymer networks

The interpenetrating polymer networks (IPNs) are recently gaining attention as sustained drug delivery systems because they could ensure a proper combination of functionality and network density to control the drug release profiles. This study aims to reveal how the functionality of two IPNs based on polyacrylamide and respectively poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) influences their smart behavior as well as their properties as delivery systems of the cationic drug verapamil hydrochloride (VPM). The “extra” α‐methyl group of PMAA results into a loss of the temperature sensitivity in the studied region and changes the pH responsivity of the PMAA/PAAM IPNs as compared to the PAA/PAAM IPNs. Moreover, the VPM diffusion in both IPNs depends on their composition due to the change in their functionality as well as of their network density. The “extra” α‐methyl group of PMAA defines its enhanced hydrophobicity and hence influences the VPM diffusion mechanism. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45380.     

Semi-solid materials for controlled release drug formulation: current status and future prospects

Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semisolid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.