具有尺寸和电荷选择性多功能分子吸附能力的电荷可转变型金属-有机框架材料

通过研究具有两种轮桨状构筑基元和四种纳米笼子结构锌基金属-有机框架(Zn-MOF)的染料吸附特性和机理,发现其分子吸附的普适性, 以及尺寸和电荷的选择性。由于Zn-MOF孔道内漂浮着抗衡阴离子, 及框架上有可配位位点, 所以它能通过离子交换机理吸附阴性染料、框架上电荷转变机理吸附阳性染料、主客体相互作用吸附中性染料, 表现出优越的分子吸附多功能性。Zn-MOF内带电荷纳米笼的尺寸选择性和电荷选择性的共同作用为设计具有更高水平兼容性和识别性的优异多孔材料铺平了道路。     

Metal-organic framework derived CoSe2 nanoparticles anchored on carbon fibers as bifunctional electrocatalysts for efficient overall water splitting

The development of efficient,low-cost,stable,non-noble-metal electrocatalysts for water splitting,particularly those that can catalyze both the hydrogen evolution reaction (HER) at the cathode and oxygen evolution reaction (OER) at the anode,is a challenge.We have developed a facile method for synthesizing CoSe2 nanoparticles uniformly anchored on carbon fiber paper (CoSe2/CF) via pyrolysis and selenization of in situ grown zeolitic imidazolate framework-67 (ZIF-67).CoSe2/CF shows high and stable catalytic activity in both the HER and OER in alkaline solution.At a low cell potential,i.e.,1.63 V,a water electrolyzer equipped with two CoSe2/CF electrodes gave a water-splitting current of 10 mA.cm-2.At a current of 20 mA.cm-2,it can operate without degradation for 30 h.This study not only offers a cost-effective solution for water splitting but also provides a new strategy for developing various catalytic nanostructures by changing the metal-organic framework precursors.     

Non-metallic nanomaterials in cancer theranostics: a review of silica- and carbon-based drug delivery systems

Abstract

The rapid development in nanomaterials has brought great opportunities to cancer theranostics, which aims to combine diagnostics and therapy for cancer treatment and thereby improve the healthcare of patients. In this review we focus on the recent progress of several cancer theranostic strategies using mesoporous silica nanoparticles and carbon-based nanomaterials. Silicon and carbon are both group IV elements; they have been the most abundant and significant non-metallic substances in human life. Their intrinsic physical/chemical properties are of critical importance in the fabrication of multifunctional drug delivery systems. Responsive nanocarriers constructed using these nanomaterials have been promising in cancer-specific theranostics during the past decade. In all cases, either a controlled texture or the chemical functionalization is coupled with adaptive properties, such as pH-, light-, redox- and magnetic field- triggered responses. Several studies in cells and mice models have implied their underlying therapeutic efficacy; however, detailed and long-term in vivo clinical evaluations are certainly required to make these bench-made materials compatible in real bedside circumstances.     

金属有机框架材料MIL-53(Al)-F127对双酚A的吸附性能

采用一步溶剂热法制备具有介孔结构金属有机框架材料MIL-53(Al)-F127，用扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X射线衍射仪(XRD)、傅里叶红外变换光谱仪(FTIR)、全自动比表面积及孔隙度分析仪(BET)等手段表征其形貌和结构，探究其对双酚A(BPA)的吸附性能并与微孔结构的MIL-53(Al)对比，研究了吸附剂的含量、pH以及温度对其吸附性能的影响。结果表明，介孔结构金属有机框架材料MIL-53(Al)-F127对双酚A具有良好的吸附性能；在pH值为6、温度为30℃条件下MIL-53(Al)-F127在20 min左右达到最大平衡吸附量为27.2 mg/g，去除率达到92%。其吸附动力学模型拟合结果，符合准二级动力学曲线。     

A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems

Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. Moreover, it has contributed to many benefits like increased residence time at application sites, drug protection, increased drug permeation and improved drug availability. In this context, investigation into the mucoadhesive properties of pharmaceutical dosage forms is fundamental, in order to characterize, understand and simulate the in vivo interaction between the formulation and the biological substrate, contributing to the development of new mucoadhesive systems with effectiveness, safety and quality. There are a lot of in vivo, in vitro and ex vivo methods for the evaluation of the mucoadhesive properties of drug delivery systems. However, there also is a lack of standardization of these techniques, which makes comparison between the results difficult. Therefore, this work aims to show an overview of the most commonly employed methods for mucoadhesion evaluation, relating them to different proposed systems and using artificial or natural mucosa from humans and animals.     

Microneedles for transdermal drug delivery: a systematic review

Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500?Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.     

Intercalated 2D nanoclay for emerging drug delivery in cancer therapy

Natural two-dimensional (2D) kaolinite nanoclay has been incorporated into an emerging drug delivery system.The basal spacing of the kaolinite nanoclay was expanded from 0.72 to 4.16 nm through the intercalation of various organic guest species of different chain lengths,which can increase the efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX).Original kaolinite (Kaolin) and the Kaolin intercalation compounds exhibited a high level of biocompatibility and very low toxicity towards cells of pancreatic cancer,gastric cancer,prostate cancer,breast cancer,colorectal cancer,esophageal cancer,and differentiated thyroid cancer.However,lung cancer and hepatocellular cancer cells need more strict compositional,structural,and morphological modulations for drug delivery carriers.DOX-Kaolin and the DOX-Kaolin intercalation compounds showed dramatically faster drug release in moderately acidic solution than in neutral condition,and exhibited enhanced therapeutic effects against ten model cancer cell cultures in a dose-dependent manner.The use of 2D nanoclay materials for a novel drug delivery system could feasibly pave a way towards high-performance nanotherapeutics,with superior antitumor efficacy and significantly reduced side effects.     

3D Printing technologies for drug delivery: a review

With the FDA approval of the first 3D printed tablet, Spritam®, there is now precedence set for the utilization of 3D printing for the preparation of drug delivery systems. The capabilities for dispensing low volumes with accuracy, precise spatial control and layer-by-layer assembly allow for the preparation of complex compositions and geometries. The high degree of flexibility and control with 3D printing enables the preparation of dosage forms with multiple active pharmaceutical ingredients with complex and tailored release profiles. A unique opportunity for this technology for the preparation of personalized doses to address individual patient needs. This review will highlight the 3D printing technologies being utilized for the fabrication of drug delivery systems, as well as the formulation and processing parameters for consideration. This article will also summarize the range of dosage forms that have been prepared using these technologies, specifically over the last 10 years.     

Microemulsions as transdermal drug delivery systems for nonsteroidal anti-inflammatory drugs (NSAIDs): a literature review

Abstract

Pain is a global crisis and significant efforts have gone into the development of drugs that can be used to treat pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of analgesics that act to selectively relieve pain and inflammation without significantly altering consciousness. Although there have been many advancements with NSAIDs drug development; these drugs still present with severe adverse effects and toxicities, which often limits their use in many patients. Moreover, others are inadequate in relieving specific types of pain such as localized or nerve pain because of poor systemic absorption with conventional delivery systems. The topical route of drug delivery has been used to avoid many of these effects, but not without challenges of its own. The skin acts as an impermeable barrier to most polar drug candidate and absorption across the dermal membranes is often too slow and incomplete to produce meaningful therapeutic benefit. Nevertheless, the use of microemulsions as topical delivery systems for small molecule drug candidates like NSAIDs has been posited as a solution to this problem for years. This review focuses on the recent use of microemulsions as a probable solution to the challenges of transdermal drug delivery of NSAIDs and how microemulsions may be used to enhance the development of more effective but safer analgesic drug products for patients.     

Gastroretentive delivery systems: a mini review

Various attempts have been made to develop gastroretentive delivery systems. For example, floating, swelling, mucoadhesive, and high-density systems have been developed to increase gastric retention time of the dosage forms. It is known that differences in gastric physiology, such as, gastric pH, and motility exhibit both intra-as well as inter-subject variability demonstrating significant impact on gastric retention time and drug delivery behavior. Nevertheless, some floating devices have shown promising results. In this paper, the gastric physiology and the reported intragastric delivery systems have briefly been presented.     

一种用于药物释控系统的微针阵列及其制作方法的研究

 通过皮肤输送药物最大的障碍是皮肤最外层的角质层．传统的静脉注射用针只有刺透皮肤深入到深层组织内部,才能有效地输送药物,这容易引起感染和疼痛,给患者造成很大的不适．介绍了一种采用硅微加工技术制作的微针,它长度适中,既能穿透皮肤的角质层,又刺激不到深层组织的神经,实现无痛注射的目的．其加工工艺是采用硅的HNA(硝酸+氢氟酸+乙酸)腐蚀系统,是一种硅的各项同性的湿法腐蚀方法．     

A Metal-Organic Framework (MOF) Fenton Nanoagent-Enabled Nanocatalytic Cancer Therapy in Synergy with Autophagy Inhibition

Nanocatalytic medicine has been developed recently to trigger intratumoral generation of highly toxic reactive oxygen species (ROS) for cancer therapy, which, unfortunately, suffers from compromised therapeutic efficacy due to a self-protective mechanism, autophagy, of cancer cells to mitigate oxidative damage. In this work, during the efforts of ROS generation by nanocatalytic medicine, a pharmacological autophagy inhibition strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. An iron-containing metal-organic framework [MOF(Fe)] nanocatalyst as a peroxidase mimic is used to catalyze the generation of highly oxidizing •OH radicals specifically within cancer cells, while chloroquine is applied to deacidify lysosomes and inhibit autophagy, cutting off the self-protection pathway under severe oxidative stress. Cancer cells fail to extract their components to detoxicate and strengthen themselves, finally succumbing to the ROS-induced oxidative damage during nanocatalytic therapy. Both in vitro and in vivo results demonstrate the synergy between nanocatalytic therapy and autophagy inhibition, suggesting that such a combined strategy is applicable to amplify tumor-specific oxidative damage and may be informative to future design of therapeutic regimen.     

Cyclosporine A: a review of current oral and intravenous delivery systems

As early as 1978, the immunosuppressive effect of cyclosporine A (CsA), a metabolite of the fungus Tolypocladium inflatum (Borel, 1989), was reported to be effective in inhibiting organ rejection in patients receiving kidney transplants from mismatched cadaver donors (Calne et al., 1978) and in the treatment of graft-versus-host disease in patients with acute leukemia following bone marrow transplants (Powles et al., 1978). Today, CsA is still indicated to prevent rejection following solid organ transplantations, prevent and treat graft-vs-host disease following bone marrow transplants, and has also been used in the treatment of autoimmune disease such as psoriasis, rheumatoid arthritis, and nephrotic syndrome (Canadian Pharmacists Association, 2006). The effectiveness of CsA is derived from its ability to specifically and reversibly inhibit immunocompetent lymphocytes in the G₀ and G₁ phase of the cell cycle. The T-helper cells are the main target, but suppression of the T-suppressor cells also occurs. The production and release of lymphokines, including interleukin-2 are also inhibited (Novartis, 2005a). CsA can be administered intravenously as well as orally in the form of a solution or a soft gelatin capsule. The following review will focus on the evolution of the emulsion-based oral formulations from the first generation as Sandimmune® to the second generation Neoral®, both products of Novartis Pharmaceutical, as well as on the Sandimmune® commercial intravenous formulation. The potential of alternative delivery systems, including micelles, micro- and nanoparticles, and liposomes, will also be discussed.     

Otic drug delivery systems: formulation principles and recent developments

Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.     

Hyaluronidase-triggered anticancer drug and siRNA delivery from cascaded targeting nanoparticles for drug-resistant breast cancer therapy

Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor (CTGF)-overexpressing breast cancer.By co-embedding the breast tumor cell-penetrating peptide (PEGA-pVEC) and hyaluronic add (HA) as a targeting media,novel cascaded targeting nanoparticles (HACT NPs) were created on a rattle mesoporous silica (rmSiO2) scaffold for the pinpoint delivery of siRNAs along with an anticancer drug,aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo.The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide,cascaded by receptor-mediated endocytosis with the aid of another targeting agent,HA,presenting a greater in vivo tumor targeting ability than single targeting ligand vectors.In addition,an HA shell prevented the leakage of therapeutic drugs during the cargo transport process,until the hyaluronidase (HAase)-triggered degradation upon lysosomes entering,guaranteeing a controllable drug release inside the target cells.When the protective shell disintegrates,the released siRNA took charge to silence the gene associated with drug resistance,CTGF,thus facilitating doxorubicin-induced apoptosis.The cascaded targeting media (PEGA-pVEC and HA) advances precision-guided therapy in vivo,while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an effident strategy for the treatment of drug resistance cancers.     

Local antibiotic delivery systems for the treatment of osteomyelitis – A review

Osteomyelitis, an inflammatory process accompanied by bone destruction, is caused by infective microorganisms. The high success rates of antimicrobial therapy by conventional routes of administration in controlling most infectious diseases have not yet been achieved with osteomyelitis for several reasons. Local and sustained availability of drugs have proven to be more effective in achieving prophylactic and therapeutic outcomes. This review introduces osteomyelitis – its present options for drug delivery and their limitations, and the wide range of carrier materials and effective drug choices. Local drug delivery for osteomyelitis is a topic of importance for more than 20 years. Carrier materials used for local delivery of antibiotics may be classified as nonbiodegradable and biodegradable. Commonly used non biodegradable carrier materials are polymethyl methacrylate (PMMA), Acrylic beads, PMMA bone cement etc. and biodegradable materials are hydroxyapatite block, bioactive glass ceramics, collagen sponge, polylactide/ployglycolide implants. Both the systems release antibiotic at concentrations exceeding the minimum inhibitory concentrations (MICs) for the most common pathogens involved in osteomyelitis without causing any adverse systemic effects although non biodegradable beads are to be removed from the surgical site after completion of antibiotic release.     

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71?nm. The highest drug loading was observed with SNEDDS-F6 of ～45?mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.     

Anti prostate cancer using PEGylated bombesin containing,cabazitaxel loading nano-sized drug delivery system

Context: Prostate cancer (PCa) is the second most-frequently diagnosed cancer in men. Cabazitaxel was approved for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.

Objective: In this study, bombesin (BN), a ligand reported to specifically target GRP overexpressing prostate tumor, was applied for the construction of lipid-polymer hybrid nanoparticles (LPNs), and used for the targeted delivery of cabazitaxel (CAB) to prostate cancer.

Methods: BN-polyethylene glycol-1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (BN-PEG-DSPE) was synthesized. CAB loaded, BN-PEG-DSPE contained LPNs (BN-CAB-LPNs) were prepared. Their particle size, zeta potential and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study of BN-CAB-LPNs was tested in LNCaP human prostatic cancer cell line (LNCaP cells). In vivo anti-tumor efficacy of the carriers was evaluated on mice bearing prostate cancer model.

Results: The optimum BN-CAB-LPNs formulations had a particle size of 184.9?nm and a 26.5?mV positive surface charge. The growth of LNCaP cells in vitro was obviously inhibited. BN-CAB-LPNs also displayed better anti-tumor activity than the other formulations in vivo.

Conclusion: The results demonstrated that BN-CAB-LPNs can sufficiently deliver CAB to the cancer cells and enhance the anti-tumor capacity. Thus, BN-CAB-LPNs can be proved to be a superior nanomedicine which can achieve better therapeutic efficacy of prostate tumor.