喜树碱-环糊精-纳米金自组装制剂的制备及抗肿瘤活性初探

首先在金纳米粒子表面修饰了α-环糊精(α-CD),并利用α-CD与难溶性药物喜树碱的主客体包合,成功得到了一种新型的金粒子喜树碱增溶制剂(CPT-αCD/AuNPs)。研究表明,CPT-αCD/AuNPs的增溶效果可达29.04μg/m L,优于绝大多数载体;载体本身生物相容性良好。并且,金粒子-药物的多价效应和增溶效应的双重作用使这种新型体系表现出远优于自由喜树碱(CPT)和单纯环糊精包合CPT的癌细胞杀灭效果。     

水溶性聚乙烯醇作为药物载体材料的应用研究

聚乙烯醇(PVA)是一种水溶性高分子聚合物,常用于眼用制剂、口服制剂、注射剂、微胶囊剂、透皮贴剂、缓释微球及纳米粒等药物载体材料的制备.介绍了水溶性聚乙烯醇材料的特性及型号,以及永溶性PVA作为药物载体材料在制剂及其它药学方面的应用,展望了PVA材料在药物载体材料方面的应用,指出了今后的发展方向和趋势.     

被动靶向药物载体的研究进展

近年来,为了提高药物载体的靶向性,国内外进行了广泛研究,被动靶向给药系统已成为给药系统研究的热点.主要介绍了被动靶向给药系统的机理、重要性及几种典型的被动靶向制剂,并对被动靶向药物载体:脂质体、毫微粒、乳剂、微泡的优缺点进行了详细的分析,提出了被动靶向制剂的发展趋势和前景.     

用于药物载体系统的多糖材料的修饰方法

癌症是一种致死率极高的全球性疾病。迄今为止,化学药物疗法仍然是治疗癌症最为直接有效的手段,然而,目前采用的化疗药物通常不具备特异性,在杀死肿瘤细胞的同时也会对正常组织细胞带来严重的毒副作用。因此,如何安全有效地将抗癌药物输送至肿瘤组织并增强药物在肿瘤细胞内的吸收是当今癌症治疗领域急需解决的难题。药物控制释放技术通过功能化载体材料对药物进行负载,对药物释放位点及速率进行控制,从而实现降低药物毒副作用、提高药物生物利用度的目的。载体材料是实现药物控制释放的技术关键,因此,设计并开发多功能药物载体已成为该领域的研究热点。理想的药物载体通常需具备高稳定性、低生物毒性、非免疫原性及组织靶向性等特点。目前,无机纳米粒子、脂质体、水凝胶、聚合物胶束、微囊等多种药物载体已被广泛应用于癌症的诊断及治疗研究。基于天然高分子材料的药物载体因具有优良的生物相容性及临床应用前景受到了众多研究者的青睐,因此,对天然高分子材料进行化学修饰构建药物载体也已成为药物控释领域的重要研究方向。多糖是一类具有良好生物降解性及生物相容性的天然高分子材料,具有在自然界中种类丰富、水溶性高、容易进行化学修饰等优点。多糖的分子结构中含有大量的活性反应基团(羟基、氨基和羧酸基团等),经过特定的化学修饰,改变其物理或化学性质可形成水凝胶、胶束、囊泡等结构,其作为药物载体在生物材料领域具有潜在的应用价值。目前,常用的多糖修饰方法包括疏水性分子接枝、醛基化改性、原位二硫键修饰等。修饰后形成的基于多糖的药物载体具有药物释放速度可控、生物安全性好等特性,并且可以实现改变药物进入人体的方式及在体内的分布,被动或主动靶向将药物输送到特定的作用部位,达到靶向治疗的目的。本文综述了多种对天然多糖进行化学修饰,构建水凝胶、胶束及囊泡类多糖药物载体的方法,并简要讨论了基于多糖的药物载体在生物医学领域的研究前景及应用价值。     

磁性脂质体的制备及应用

磁性脂质体是掺入磁性载体材料的脂质体,由于其良好的载药性、磁靶向性以及生物相容性而受到广泛的研究.综述了磁性脂质体的制备方法,总结了磁性脂质体在靶向药物、热化疗、造影剂领域中的应用研究进展最后展望了磁性脂质体的发展方向.     

树枝状大分子PAMAM及其复合物在药物/基因载体方面的研究进展

主要介绍了PAMAM的两种主要载药机制(物理包埋作用、静电和共价作用)和PAMAM及其复合物对难溶性药物的增溶和缓控释等方面的研究进展,简要介绍了其在基因载体方面的研究进展,最后结合自身的研究情况展望了其未来的发展趋势。     

靶向型药物载体在抗肿瘤治疗中的研究进展

恶性肿瘤是一种严重威胁人类健康的常见病和多发病,是引起死亡的主要原因之一。近年来,抗肿瘤药物的靶向性研究越来越受到人们的重视。发展抗肿瘤药物的新型靶向载体,增加药物靶向性,提高生物利用度,降低毒副作用,是目前备受关注的课题。根据近年来文献,综述了一些新型的抗肿瘤药物载体,包括靶向的脂质体载药系统、纳米粒载药系统、微粒载药系统、胶束载药系统等,并分别总结了其颗粒大小、载药类型、载药模式及治疗效果等,为肿瘤的靶向给药研究提供思路。     

树状大分子作为药物载体的研究新进展

树状大分子作为药物载体是目前分子药剂学研究的热点.综述了树状大分子作为药物载体发展的几个阶段、载药方式,以及其作为药物裁体在增溶、缓释、靶向等方面的应用,展望了树状大分子作为药物载体的发展趋势.     

磁性水凝胶作为药物载体的应用研究进展

磁性水凝胶是一类同时具有磁性材料、高分子材料及水凝胶的性质特点的无机/有机复合材料。因具有优良的磁学性能及生物相容性,其作为新一代的药物载体可以实现磁响应、磁靶向及磁热疗等功能,在药物控制释放领域具有广阔的应用前景。对磁性水凝胶的制备方法及其在药物载体领域的研究情况进行了综述,详细介绍了磁性水凝胶作为药物载体的两种药物释放机理(ON/OFF模型及热敏释放原理),及其在磁靶向药物控释、磁热疗和磁共振成像方面的应用研究现状。     

如何制备靶向效率更高的纳米药物?

正化疗是一种重要的癌症治疗手段,但是化疗药物往往具有严重的毒副作用且很难达到令人满意的治疗效果,因而其在临床上的应用仍有待改善。肿瘤靶向药物递送是一种极具潜力的新型治疗手段,该类技术能有效增加化疗药物在靶部位的浓度同时降低其在健康组织器官内的蓄积,最终提高化疗的疗效和安全性。在众多靶向药物递送载体中,聚合物胶束是目前应用最广泛且最成功的载体之一。聚合物胶束是由两亲性嵌段共聚物通过自组装形成的纳米级药物载体,具有一个亲水性的外     

Nanostructured cochleates: a multi-layered platform for cellular transportation of therapeutics

Among lipid-based nanocarriers, multi-layered cochleates emerge as a novel delivery system because of prevention of oxidation of hydrophobic and hydrophilic drugs, enhancement in permeability, and reduction in dose of drugs. It also improves oral bioavailability and increases the safety of a drug by targeting at a specific site with less side effects. Nanostructured cochleates are used as a carrier for the delivery of water-insoluble or hydrophobic drugs of anticancer, antiviral and anti-inflammatory action. This review article focuses on different methods for preparation of cochleates, mechanism of formation of cochleates, mechanism of action like cochleate undergoes macrophagic endocytosis and release the drug into the systemic circulation by acting on membrane proteins, phospholipids, and receptors. Advanced methods such as calcium-substituted and β-cyclodextrin-based cochleates, novel techniques include microfluidic and modified trapping method. Cochleates showed enhancement in oral bioavailability of amphotericin B, delivery of factor VII, oral mucosal vaccine adjuvant-delivery system, and delivery of volatile oil. In near future, cochleate will be one of the interesting delivery systems to overcome the stability and encapsulation efficiency issues associated with liposomes. The current limiting factors for commercial preparation of cochleates involve high cost of manufacturing, lack of standardization, and specialized equipments.     

Profiling of drugs for membrane activity using liposomes as an in vitro model system

The increasing size of chemical libraries being analyzed by high-throughput screening results in a growing number of active compounds that need to be assessed before moving forward in the drug development process. As a consequence, more rapid and highly sensitive strategies are required to accelerate the process of drug discovery without increasing the cost. Due to the fact that significant numbers of compounds from combinatorial libraries are hydrophobic in nature, approaches are needed to evaluate the potential for these compounds to interfere with the functions of biological membranes. The liposome system was used to detect agents that act as follows: (i) ionophores able to induce specific ion permeability, e.g., valinomycin for K⁺ and protonophoric uncouplers for H⁺; (ii) ion antiporters which exchange H⁺ for other ions, e.g., nigericin; (iii) agents that form low specificity ion channels in the membrane, e.g., gramicidin; and (iv) detergents and other membrane-disrupting agents. We propose using this liposome assay during the drug development process to identify compounds that have membrane activity and, as a consequence, produce a biological effect by altering the physico-chemical properties of the cell membrane rather than interacting with a protein target. Screening of a representative set of biologically-active compounds (198) indicated that the majority of systemic antimicrobial drugs, but not topical drugs, lack membrane activity in this model system.     

Multifunctional nanoparticles, nanocages and degradable polymers as a potential novel generation of non-invasive molecular and cellular imaging systems

In recent years, polymeric scaffolds have been used in several biomedical applications for delivery of drugs or other biologically relevant molecules. Polymeric nanostructures display different (and in some cases more powerful) properties respect to bulk materials. This, lead academic researchers and industry to cooperate in developing pioneering nanostructured materials for industrial and biomedical applications. Moreover, the preparation and use of systems with multiple (multifunctional) properties (i.e., bioconjugation with superparamagnetic, fluorescent or targeting molecules) is positioned to become a viable and innovative tool for application in several clinical fields. Other nanostructured systems like nanocages and degradable nanoparticles, are emerging as potential innovative systems that could be exploited as multifunctional delivery vectors. This brief critical review is aimed at collecting and discussing some recent patents dealing with the preparation and use of multifunctional nanoparticles, nanocages and degradable nanoparticles in biomedicine and non-invasive bioimaging applications. Perspectives for a potential use of these multifunctional nanosystems in pediatries have been also discussed.     

Chrysin-loaded folate conjugated PF127-F68 mixed micelles with enhanced oral bioavailability and anticancer activity against human breast cancer cells

Chrysin (CH), a phytoconstituent has numerous pharmacological activities including anticancer activity. However, CH suffers from a drawback of poor aqueous solubility and in turn poor bioavailability limiting its clinical utility. In this work CH loaded folate-conjugated pluronic PF127-pluronic F68 mixed micelles were prepared with an objective to augment oral bioavailability and cytotoxicity of CH in human breast cancer cell line MCF-7 by active targeting mechanism. Folate-conjugated PF127 was synthesized and used for preparation of CH-MM. Optimized batch (using factorial design) of CH-MM was characterized by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), atomic force microscopy (AFM), in vitro CH release, in vivo study, and in vitro cell line study. FTIR study suggested encapsulation of CH into the micelle core. CH-MM showed controlled release of CH releasing higher amount (2.5 fold) in 24?h when compared to CH alone (A-CH). Further significant increase in C_max (2 fold) and AUC_0–∞ (3 fold) for CH-MM when compared to A-CH suggested significant improvement in oral bioavailability of CH. Additionally, CH-MM showed 5 fold reduction in GI₅₀ value of CH when tested in MCF-7 cells reducing GI₅₀ value of CH significantly. CH-MM can serve as a platform carrier system for active targeting of BCS class II molecules with potential anticancer activity.     

Clinical translation of nanomedicines

This review describes the clinical translation of cancer nanomedicines based on three nanocarrier platforms: liposomes, polymeric micelles, and nanoparticles. A dozen nanomedicines are on the market, the majority (eight) based on the most mature liposome technology. The other marketed nanomedicines are based on polymeric micelles (one) and nanoparticles (one). Polymeric prodrugs account for the remaining two marketed products. Altogether a total of 41 nanocarrier-based formulations have translated from the bench to the bedside and are under investigation at different levels of clinical development. Many more nanocarrier-based formulations are in preclinical development. Not surprisingly, the vast majority of these nanomedicines (37) rely on passive targeting through the EPR (enhanced permeability and retention) effect, avoiding the additional regulatory, production, cost of goods, and polydispersity challenges of active, ligand-receptor based targeting. Only four actively targeting nanocarriers are in clinical development, one using PSMA and three using TfR as the target. It still needs to be demonstrated that active targeting of nanocarriers that are subjected to the EPR effect provides an advantage substantial enough to justify the additional efforts. The review clearly identifies the areas of successful translation of nanomedicines but also shows areas where the potential is still underdeveloped and opportunities for improvement are promising. Overall, the high expectation that has been placed in nanomedicines is showing progress, increasing the benefits and treatment options for cancer patients.     

Effect of powder substrate on the dissolution properties of methyclothiazide liquisolid compacts

The effects of powder substrate composition on the in vitro release properties of methyclothiazide liquisolid compacts were evaluated. The dissolution patterns of this water-insoluble drug formulated in liquisolid tablets were also compared to those of commercial products. According to the new liquisolid technique, liquid medications such as solutions or suspensions of water-insoluble drugs in suitable nonvolatile liquid vehicles can be converted into acceptably flowing and readily compressible powders by a simple admixture with certain powder substrates, which are selected powders referred to as the carrier and coating materials. Enhanced release profiles may be exhibited by such systems due to the increased wetting properties and surface of drug available for dissolution. Liquisolid tablets of methyclothiazide containing a 5% w/w drug solution in polyethylene glycol 400 were prepared using powder substrates of different excipient ratios. The release rates of such products were assessed using the USP dissolution test and were compared to those of their commercial counterparts. It was observed that maximum drug dissolution rates can be exhibited by systems that have powder substrates with optimum carrier-to-coating ratios. In addition, liquisolid tablets displayed significantly enhanced dissolution profiles compared to those of marketed products.     

Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: opportunities and challenges

Porous silica-based drug delivery systems have shown considerable promise for improving the oral delivery of poorly water-soluble drugs. More specifically, micro- and meso-porous silica carriers have high surface areas with associated ability to physically adsorb high-drug loads in a molecular or amorphous form; this allows molecular state drug release in aqueous gastrointestinal environments, potential for supersaturation, and hence facilitates enhanced absorption and increased bioavailability. This review focuses primarily on the ability of porous silica materials to modulate in vitro drug release and enhance in vivo biopharmaceutical performance. The key considerations identified and addressed are the physicochemical properties of the porous silica materials (e.g. the particle and pore size, shape, and surface chemistry), drug specific properties (e.g. pKa, solubility, and nature of interactions with the silica carrier), potential for both immediate and controlled release, drug release mechanisms, potential for surface functionalization and inclusion of precipitation inhibitors, and importance of utilizing relevant and effective in vitro dissolution methods with discriminating dissolution media that provides guidance for in vivo outcomes (i.e. IVIVC).     

Microwave generated nanocomposites for making insoluble drugs soluble

In order for a drug to be bioavailable the human body must absorb it, and in oral treatments absorption takes place, after drug dissolution, by diffusion of the molecules through the gastrointestinal (GI) membranes. Since the GI tract is an aqueous environment and more than one third of the existing drugs are poorly soluble or insoluble in water, solubilization of water-insoluble drugs is a big issue of pharmaceutical research. The key-concept of solubilization is to force the insoluble solid to assume a (metastable) microstructure characterized by nanoscale periodicity. Our research, starting from this scene, is based on the following facts: (a) the most advanced approaches to water-insoluble drugs solubilization are based on generating a drug dispersion (at molecular and/or nanoscale level) in a stabilizing media, preferably in solid-state form, (b) the polarizing aspect of microwave (MW) heating produces several specific excess effects, in particular enhanced mass transport, thus providing a green, effective tool for generating drug solid dispersions, and (c) with few exceptions pharmaceutical (organic) materials are diamagnetic and dielectric, i.e. are suitable for MW heating. We developed a method based on MW induced diffusion (MIND) for generating activated drug/3D-matrix nanocomposites. This innovative (and environmentally friendly) solid-state solubilization technique will be presented and discussed.     

盘状液晶材料及电导性能研究的最新进展

盘状液晶分子易于形成柱状相结构材料,从而具有较高的电导特性,是理想的电载流子传输材料,可用于制备光电器件。本文主要介绍苯并菲、酞菁、六苯并冠等盘状液晶材料的制备、电导性能的研究以及在器件应用研究中如纳米导线、有机太阳能电池的最新进展。     

Polyacrylamide–punicic acid conjugate‐based micelles for flutamide delivery in PC3 cells of prostate cancer: synthesis,characterisation and cytotoxicity studies

The aim of the present study was to synthesize a novel biopolymeric micelle based on punicic acid (PA) and polyacrylamide (PAM) for carrying chemotherapeutic drugs used in prostate cancer treatment. A polymer composite micelle was prepared by chemical conjugation between PAM and PA. The micelles were prepared by self‐assembly via film casting followed by ultrasonication method. The successful production of PAMPA copolymeric micelles was confirmed using FTIR, 1H‐NMR, and TEM. Then, flutamide was loaded in the designed nanomicelles and they were characterized. The cell cytotoxicity of the micelles was studied on PC3 cells of prostate cancer. The prepared nanomicelles showed the particle size of 88 nm, PDI of 0.246, zeta potential of −9 mV, drug loading efficiency of 94.5%, drug release of 85.6% until 10 hours in pH 7.4 and CMC of 74.13 μg/ml. The cell viability in blank nanocarriers was about 70% in PC3 cells at concentration of 25 μM. More significant cytotoxic effects were seen for flutamide loaded micelles at this concentration compared to the free drug. The results suggest that the PAMPA co‐polymeric nanomicelles can be utilized as an effective carrier to enhance the cytotoxic effects of flutamide in prostate cancer.Inspec keywords: nanoparticles, cellular biophysics, drugs, biomedical materials, drug delivery systems, colloids, hydrophilicity, pH, transmission electron microscopy, particle size, cancer, casting, toxicology, electrokinetic effects, polymer blends, proton magnetic resonance, nanomedicine, self‐assembly, nanofabrication, Fourier transform infrared spectraOther keywords: PC3 cells, chemotherapeutic drugs, prostate cancer treatment, polymer composite micelle, chemical conjugation, proton nuclear magnetic resonance, cell cytotoxicity, prepared nanomicelles, drug loading efficiency, drug release, critical micelle concentration, cell viability, cytotoxic effects, flutamideloaded micelles, flutamide delivery, polyacrylamide‐punicic acid conjugate‐based micelles, PAMPA copolymeric nanomicelles, biopolymeric micelle, PAM‐punicic acid copolymer copolymeric micelles, hydrophilic shell, self‐assembly, film casting, ultrasonication method, Fourier transform infrared spectra, transmission electron microscopy, particle size, polydisperity index, zeta potential, pH, blank nanocarriers, time 10.0 hour