Enabling anticancer therapeutics by nanoparticle carriers: the delivery of Paclitaxel

Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy.     

排汗冷却材料用于人体舒适度调节的技术原理及进展

拥有排汗冷却技术的织物材料可以提高排汗效率,提高人体热舒适性。概述了织物面料排汗冷却技术的主要特征及实现原理,包括快速吸汗、快速排汗和提高透气性;详述了新型排汗冷却材料,包括吸湿快干纤维、表面张力驱动微流体排汗材料、水驱动形状记忆聚合物材料、吸湿膨胀多层复合材料和湿度梯度响应聚合物材料;介绍了排汗冷却材料应用在功能性衣物上的商业化进展;最后总结了各种排汗冷却技术的优缺点,并对未来研究和发展方向提出了建议。     

Drug-Delivery Systems for Tunable and Localized Drug Release

Drug-delivery systems can be designed to provide localized drug release with a variety of customizable release profiles. Passive systems enable sustained, zero-order release for days or weeks, while remotely triggered systems enable the timing and dose of drug release to be controlled by the patient or physician. Release profiles can be engineered to match the requirements of particular ailments. We review on-demand drug-delivery systems that release a therapeutic in response to magnetic, near-infrared, or UV fields; such systems could extend the capabilities of sustained release systems by incorporating programmed dosing regimens.     

Design and Encapsulation of Immunomodulators onto Gold Nanoparticles in Cancer Immunotherapy

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.     

Enhancement of bioactivity and bioavailability of curcumin with chitosan based materials

Curcumin (CUR) has been investigated for its poor accessibility to a site of action or absorption and rapid metabolism to cope with the limited medication and cure applications. This article reviews numerous approaches, such as encapsulated surfactant/polymeric micelles, liposomes, micro/nano-spheres, nano-suspensions/composites, nanocomplex, films, and hydrogels for effective transfer of CUR to target sites. Chitosan (CS), and chitosan derivatives have been found to enhance therapeutic efficacy of CUR. CS/modified-CS based alginate, cyclodextrin, starch, dextran sulfate, ZnO, phytosomes, and poly(butyl) cyanoacrylate drug delivery matrices improved bioavailability, prolonged drug loading and permeability, sustained release rate, improved solubility and stability (prevent metabolic degradation) of CUR, consequently promoting various clinical applications. CS based polysaccharide, protein, and metal oxide drug delivery nano formulations advantageously participated to improve biological activities of CUR. We have attempted to summarize these delivery approaches, and reviewed future trends/strategies to permit the introduction of CUR as practical therapeutic drug.     

How implementation of Quality by Design and advances in Biochemical Engineering are enabling efficient bioprocess development and manufacture

In recent years, Quality by Design (QbD) has gained significant prominence in the pharmaceutical industry as an efficient way of designing and controlling processes used to make therapeutic products. At its heart, QbD seeks to identify an operating envelope within which production consistently satisfies a target product quality profile and thereby achieves the desired level of safety and efficacy. Such an approach is assisted by a range of Biochemical Engineering techniques which increase process and product understanding. This perspective describes how the principles of Quality by Design and developments in the field of Biochemical Engineering are providing the pharmaceutical sector with a toolbox of methods that enable efficient bioprocess development and manufacture. Copyright © 2011 Society of Chemical Industry     

The development of coatings using combinatorial/high throughput methods: a review of the current status

Combinatorial chemistry is a relatively new experimental methodology developed by academics and researchers in the pharmaceutical industry to reduce the time and cost associated with drug development. Basically, combinatorial chemistry involves the rapid synthesis and evaluation of large numbers of compounds in parallel using robotics, rapid analytical instrumentation, and data management software. More recently, the principles of combinatorial chemistry have been applied to materials development, and interest in this area is increasing rapidly. This interest can be attributed to the potential for obtaining a major competitive advantage by implementing a combinatorial approach. This document provides an introduction to combinatorial materials science and provides a review of efforts aimed at developing combinatorial workflows for coating development. While the application of combinatorial methods to coating development is still in its infancy, full combinatorial workflows have been developed within a few different organizations. Presented at the 2006 FutureCoat! conference, sponsored by the Federation of Societies for Coatings Technology, in New Orleans, LA, on November 1–3, 2006.     

新型DPP-4抑制剂LGT-6在Caco-2细胞单层模型中的转运特性研究

通过建立Caco-2细胞单层模型探究降糖化合物LGT-6的转运特性。采用MTS法测定LGT-6的安全浓度范围,通过测定跨膜电阻、碱性磷酸酶活力、高渗透性药物普莱洛尔与低渗透性药物荧光素钠通透性实验的表观渗透系数P_app(AP→BL)来验证Caco-2细胞单层模型的致密性。考察LGT-6在从Transwell顶端(AP)到底端(BL)及底端到顶端的转运特性,计算表观渗透系数和外排比。分析转运时间、给药浓度和P-糖蛋白(P-gp)抑制剂对LGT-6转运特性的影响。Caco-2细胞单层模型建立成功,可用于LGT-6的转运特性研究。LGT-6的转运量随时间的延长及浓度的增大而增加,不同浓度的LGT-6在双向转运随浓度变化而变化,从AP→BL的P_app值为3.55×10^-6~5.64×10^-6cm/s,BL→AP的P_app为4.28×10^-6~8.76×10^-6cm/s,外排比(ER)均≥1.2。降糖化合物LGT-6在体外Caco-2细胞模型上的口服吸收较好,其转运方式主要以被动扩散为主,可能有P-糖蛋白参与其转运。     

Processing vegetable oils using nonporous denser polymeric composite membranes

Membrane processing offers several advantages over conventional processes for edible oil refining. In recent years, processing solvent-extracted, screw-pressed, and used frying oils using nonporous denser polymeric composite membranes without pretreatment and addition of chemicals has been extensively investigated. In the present review, results obtained with real and model systems have been summarized and a comprehensive explanation is provided on the mechanism of rejection and differential permeation of oil constituents. Phospholipid-TG and pigment-TG systems are construed as conventional solute-solvent systems, and tocopherol-TG and FFA-TG systems are treated as liquid mixtures exhibiting differential permeability. Dense membrane theory appears more applicable than the reverse osmosis theory in qualitatively explaining the differential permeability of liquid constituents of the oil. Membrane processing of oils appears to have the potential to be a one-step process, especially for screw-pressed oils, in producing a premium-quality product. However, the development of suitable membranes that enable higher fluxes is necessary for industrial adoption of this technology.     

MCM-41 for furosemide dissolution improvement

The ordered mesoporous silica material MCM-41 was used to prepare a novel drug delivery system (DDS) for oral administration of the diuretic furosemide (FURO), labeled in class IV of the Biopharmaceutics Classification System (BCS). This drug is characterized by both low solubility and permeability and its absorption window is the stomach and the proximal small intestine. Thus, the aim of this work was the development of an immediate formulation that could improve the drug release in its preferential absorptive regions.Three inclusion products MCM-41-FURO-E/D, MCM-41-FURO-S and MCM-41-FURO-E have been prepared in three different ways in order to find the best preparation conditions. They were characterized by XRPD, DSC, FT-IR, TGA and B.E.T. and then the inclusion products displaying the best characteristics were submitted to in vitro studies. They evidenced that the examined inclusion products displayed FURO dissolution enhancement, followed by a complete release within 90 min. Moreover, physical stability studies revealed that MCM-41 is able to stabilize the drug preventing it from re-crystallization. At last, as FURO is light sensitive, the effect of MCM-41 on drug photochemical stability was also investigated and the results indicated the protective action exerted by the matrix.     

Characterization of mixing in an optimized designed T-T mixer with cylindrical elements

Passive micromixers are preferred over active mixers for many microfluidic applications due to their relative ease in integration into complex systems and operational flexibility. They also incur very low cost of manufacturing. However, the degree of mixing is comparatively low in passive mixers than active mixers due to the absence of disturbance in the flow by external forces and the inherent laminar nature of microchannel flows. Various designs of complex channel structures and three-dimensional geometries have been investigated in the past to obtain an efficient mixing in passive mixers. But the studies on mixing enhancement with simple planar geometries of passive mixers have been few and limited. The present work aims to investigate the possibility of mixing enhancement by employing simple planar type designs, such as T-mixer and T-T mixer with cylindrical elements placed in the mixing channel. The mixing performance has been evaluated in the Reynolds number range of 6 to 700. Numerical results have shown that T-T mixer with cylindrical elements performed significantly well and obtained very good mixing quality over basic T-mixer for the entire range of Reynolds number (6 to 700). The device has also shown better mixing as compared to basic T-T mixer and T-mixer with cylindrical elements. A larger pair of vortices formed in the stagnation area due to the presence of a cylindrical element in the junction. Cylindrical elements downstream caused significant enhancement in mixing due to splitting and recombining action. The size of the cylindrical element in the T-T mixer has been optimized to obtain better mixing performance of the device. Remarkable improvement in mixing quality by T-T mixer with cylindrical elements has been obtained at the expense of small rise in pressure drop as compared to other passive designs considered in this study. Therefore, the current design of T-T mixer with cylindrical elements can act as an effective and simple passive mixing device for various micromixing applications.     

Translating Research for the Radiotheranostics of Nanotargeted 188Re-Liposome

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted ¹⁸⁸Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted ¹⁸⁸Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest ¹⁸⁸Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.     

Development and validation of system design principles for water reuse systems

Decision support software (DSS) for Water Treatment for Reuse with Network Distribution (WTRNet) has been developed within the AQUAREC project on “Integrated Concepts for Reuse of Upgraded Wastewater”, under the Fifth European Community Framework Programme. The overall objective of work conducted as part of the AQUAREC project has been the development and validation of system design principles for water reuse systems. The DSS provides an integrated framework for optimisation of treatment and distribution aspects of water reuse and the selection of end-users, and has been used in the development of the design principles. The principle components of the software (simulation and optimisation models) are presented, followed by the discussion on the software validation. A case study is then illustrated, on which WTRNet has been applied to develop least-cost design alternatives. Design principles for water reuse systems that were achieved by applying the WTRNet tool are presented, in which the importance of utilising formal optimisation in determining the most promising design alternatives is demonstrated.     

微混合器内流体混合的研究进展

Microreaction technology is one of the most innovative and rapid developing fields in chemical engineering, synthesis and process technology. Many expectations toward enhanced product selectivity, yield and purity, improved safety, and access to new products and processes are directed to the microreaction technology. Microfluidic mixer is the most important component in microfluidic devices. Based on various principles, active and passive micromixers have been designed and investigated. This review is focused on the recent developments in microfluidic mixers. An overview of the flow phenomena and mixing characteristics in active and passive micromixers is presented, including the types of physical phenomena and their utilization in micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, T-micromixer is highlighted as an example to illustrate the effect of design and operating parameters on mixing efficiency and fuid flow inside microfluidic mixers.     

New prodrugs of the antiprotozoal drug pentamidine

Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central nervous system (CNS) penetration. This work deals with the development and systematic characterisation of new prodrugs of pentamidine. For this reason, numerous prodrugs that use different prodrug principles were synthesised and examined in vitro and in vivo. Another objective of the study was the determination of permeability of the different pentamidine prodrugs. While some of the prodrug principles applied in this study are known, such as the conversion of the amidine functions into amidoximes or the O-alkylation of amidoximes with a carboxymethyl residue, others were developed more recently and are described here for the first time. These newly developed methods aim to increase the affinity of the prodrug for the transporters and mediate an active uptake via carrier systems by conjugation of amidoximes with compounds that improve the overall solubility of the prodrug. The different principles chosen resulted in several pentamidine prodrugs with various advantages. The objective of this investigation was the systematic characterisation and evaluation of eight pentamidine prodrugs in order to identify the most appropriate strategy to improve the properties of the parent drug. For this reason, all prodrugs were examined with respect to their solubility, stability, enzymatic activation, distribution, CNS delivery, and oral bioavailability. The results of this work have allowed reliable conclusions to be drawn regarding the best prodrug principle for the antiprotozoal drug pentamidine.     

基于卟啉的药物活性化合物的合成研究进展

综述了十几年来基于卟啉的药物活性物质的设计思路和合成方法,重点介绍了基于卟啉的光敏剂及二元活性化合物的合成.同时,展望了卟啉类药物活性化合物合成领域的未来发展趋势.     

Cell-Penetrating Peptide Foldamers: Drug-Delivery Tools

Highly efficient drug-delivery tools for membrane-impermeable compounds, proteins, and nucleic acids in living cells are useful in the fields of chemical biology and drug discovery, and such tools have been widely studied. One strategy in the development of novel drug-delivery tools is to utilize cell-penetrating peptide (CPP) foldamers. CPP foldamers are folded oligopeptides that possess cell membrane permeability. In recent decades, a wide variety of CPP foldamers have been reported by many groups. Herein, CPP foldamers are introduced and discussed from the viewpoints of component monomers (amino acids) and their application as drug-delivery tools.     

Study on Biopharmaceutics Classification and Oral Bioavailability of a Novel Multikinase Inhibitor NCE for Cancer Therapy

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (P_eff) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10⁻⁴ mg·min⁻¹·cm⁻². The P_eff value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates.     

己烷油装置储运系统增上油气回收系统的可行性分析

简述了己烷油装置配套的储运系统现状,综述了低温冷凝法、活性炭吸附法、溶解吸收法、膜选择渗透法以及氧化燃烧法五种油气回收技术的原理,评价对比其中四种技术的尾气排放情况、二次污染情况、安全运行状态、设备工艺复杂程度等指标,根据各单一技术的优缺点,探讨了冷凝法和吸附法相结合、冷凝法和膜分离法相结合的两种较为实用的油气回收复迭技术,简述了其工作原理。对己烷油装置的储运系统提出改进建议,得出增上油气回收系统的可行性结论。     

Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic applications

Clever combinations of different types of functional nanostructured materials will enable the development of multifunctional nanomedical platforms for multimodal imaging or simultaneous diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) possess unique structural features such as their large surface areas, tunable nanometer-scale pore sizes, and well-defined surface properties. Therefore, they are ideal platforms for constructing multifunctional materials that incorporate a variety of functional nanostructured materials. In this Account, we discuss recent progress by our group and other researchers in the design and fabrication of multifunctional nanocomposite nanoparticles based on mesoporous silica nanostructures for applications to simultaneous diagnosis and therapy. Versatile mesoporous silica-based nanocomposite nanoparticles were fabricated using various methods. Here, we highlight two synthetic approaches: the encapsulation of functional nanoparticles within a mesoporous silica shell and the assembly of nanoparticles on the surface of silica nanostructures. Various nanoparticles were encapsulated in MSNs using surfactants as both phase transfer agents and pore-generating templates. Using MSNs as a scaffold, functional components such as magnetic nanoparticles and fluorescent dyes have been integrated within these systems to generate multifunctional nanocomposite systems that maintain their individual functional characteristics. For example, uniform mesoporous dye-doped silica nanoparticles immobilized with multiple magnetite nanocrystals on their surfaces have been fabricated for their use as a vehicle capable of simultaneous magnetic resonance (MR) and fluorescence imaging and drug delivery. The resulting nanoparticle-incorporated MSNs were then tested in mice with tumors. These in vivo experiments revealed that these multifunctional nanocomposite nanoparticles were delivered to the tumor sites via passive targeting. These nanocomposite nanoparticles served as successful multimodal imaging probes and also delivered anticancer drugs to the tumor site. With innumerable combinations of imaging modalities and drug delivery available within these vehicles, multifunctional nanocomposite nanoparticles provide new opportunities for clinical diagnostics and therapeutics.