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Neutrophils are the first to reach the site of infection as they are the most numerous and dominant pathogen-killing cells in the circulatory system. They are both involved in initial immunity and act as effector cells in destructive inflammatory responses. The abundance of neutrophils in the human body and their inherent properties give them the ability to target inflammatory sites for drug delivery, and their important role in the inflammatory response has led to increasing attention to the therapeutic potential of neutrophils. In this review paper, the research progress in neutrophil-mediated drug delivery systems is reviewed, including the use of neutrophils as carriers, neutrophil exosomes as carriers, and in vivo targeted delivery of drugs using neutrophil properties.
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Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.
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Animals , Drugs, Chinese Herbal/chemistry , Plants, Medicinal , Antioxidants , Anti-Inflammatory Agents , Drug CarriersABSTRACT
BACKGROUND: Based on enhanced permeability and retention effect of nanoscale drug delivery systems in tumors, intelligent design of anti-tumor drug delivery vehicles has recently become a major direction in the development of tumor treatment strategies. Among them, the enzyme-responsive nano-delivery system has played a relatively important role, taking tumor-specific and highly expressed enzymes as precise targets so as to greatly improve targeting performance. OBJECTIVE: To summarize researches on the protocol, targeting efficiency and anti-tumor effects of enzyme-responsive nanoparticles in cancer treatment in recent years. METHODS: PubMed, Web of Science, CNKI and Wanfang databases were searched for the articles concerning the enzyme-responsive nanoparticles related to tumor treatment, with the search terms of “nanoparticles; neoplasms; enzymes; drug carriers; responsive” in English and Chinese, respectively. After initial screening of all articles according to inclusion and exclusion criteria, those with higher relevance were retained for the successive review. RESULTS AND CONCLUSION: Currently, enzyme-responsive nanoparticles are classified into two basic types in the article: drug-releasing type and functional type. Both are further divided into several sub-categories. Different designs target at corresponding tumors and their microenvironment characteristics. Among them, drug-releasing enzyme-responsive nanoparticles are designed to achieve controlled release of drugs at specific sites in tumors by enzyme response, while functional enzyme-responsive nanoparticles focus on improving the targeting efficiency and accumulation of nanoparticles in tumors. Both main types achieved specific release of drugs in tumors due to corresponding enzyme response, thereby reducing systemic toxicity and improving anti-tumor effects. According to current research trends, enzyme responsiveness is gradually turning into a part of the design of multiple responsive nanoparticle antitumor drugs in coming years. More tumor-specific enzymes and response mechanisms will be discovered to cope with complex tumor types and their microenvironment as well.
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Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the
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Biocompatible Materials , Hydrogels , Micelles , Nanocomposites , PolymersABSTRACT
Muitos pacientes acometidos por infecções fúngicas sucumbem devido a não eficácia dos antibióticos ou por toxicidade dos mesmos. Anfotericina B é um dos antifúngicos mais eficientes do mercado apesar de sua alta toxicidade, tem estrutura poliênica e é um composto insolúvel em água, sendo necessário o uso de adjuvantes e novas tecnologias para preparo de formulações eficazes. Cetoconazol é um composto imidazólico, também com ação antifúngica de grande espectro de ação e difícil solubilização em meio aquouso, porém solúvel somente em baixos valores de pH. Estudos têm demonstrado a utilização de bixina na preparação de dispersões aquosas de compostos insolúveis ou pouco solúveis em água. Bixina é o principal composto das cascas de semente de Bixa orellana (urucum), sendo um carotenoide insolúvel em água, porém, permite preparações na forma de nanodispersões aquosas com incorporação de fármacos apolares ou lipofílicos. O objetivo deste trabalho foi preparar anfotericina B e cetoconazol na forma de nanodispersões a partir de bixina, utilizando pullulan e trealose como adjuvantes e avaliar estabilidade e eficácia antimicrobiana por ensaios físico-químicos e microbiológicos. Pullulan é um polissacarídeo constituído por unidades de maltotriose, com propriedades adesivas e capacidade de formar biofilmes, enquanto trealose é um composto com duas unidades de glicose, com boa estabilidade em faixas de pH de 3 a 10 e capaz de suportar altas temperaturas, como processos de esterilização por calor úmido. Ensaios físico-químicos demonstraram boa manutenção das características das preparações propostas neste projeto, como, por exemplo, diâmetro hidrodinâmico e potencial zeta das estruturas das nanodispersões de bixina e antifúngicos e também eficácia antimicrobiana frente a Candida albicans ATCC 10231. Os resultados apresentam perspectivas para aprimoramentos de formulações com fármacos pouco solúveis ou insolúveis em água, pesquisa de novos biomateriais e outras aplicações nas áreas farmacêutica e cosmética
Many patients with fungal infections succumb due to ineffectiveness or toxicity of antibiotics. Amphotericin B is one of the most efficient antifungals on the market despite its high toxicity. It presents polyenic structure and is a water-insoluble compound. In this case, it is necessary to use adjuvants and new technologies to prepare effective formulations. Ketoconazole is an imidazolic compound, also with broad spectrum antifungal action and difficult solubilization in aqueous medium but it is soluble at low pH values. Studies have demonstrated the use of bixin in the preparation of aqueous dispersions of insoluble or poorly soluble compounds in water. Bixin is the main compound of Bixa orellana (annatto) seed husks, being a water-insoluble carotenoid, but it allows preparations in the form of aqueous nanodispersions with incorporation of apolar or lipophilic drugs. The objective of this work was to prepare amphotericin B and ketoconazole as nanodispersions from bixin, using pullulan and trehalose as adjuvants and to evaluate them under aspects of stability and efficacy by physicochemical and microbiological assays. Pullulan is a polysaccharide consisting of maltotriose units with adhesive properties and ability to form biofilms, while trehalose is a compound with two glucose units with good stability at pH ranges from 3 to 10 and capable of withstanding high temperatures such as processes of sterilization by moist heat. Physicochemical tests demonstrated good maintenance of the characteristics of the preparations proposed in this project, such as hydrodynamic diameter and zeta potential of bixin and antifungal nanodispersions and also antimicrobial efficacy against Candida albicans ATCC 10231. The results present prospects for improvement. of poorly soluble or water-insoluble drug formulations, research on new biomaterials and other applications in the pharmaceutical and cosmetic fields
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Trehalose , Amphotericin B/agonists , Growth and Development , Ketoconazole/adverse effects , Anti-Bacterial Agents/analysis , Patients , Pharmaceutical Preparations/analysis , Antifungal Agents/pharmacokineticsABSTRACT
Microfluidic technology is a scientific technology that precisely controls and manipulates fluids in micro-nano-scale space, and has become one of the research hotspots in the field of nanomedicine. It has the ability to scale the basic functions of biological and chemical laboratories, including sample preparation, reaction, separation and detection, to a few square centimeters of chip. Compared with traditional approaches, microfluidic technology is equipped with many advantages in the development of nanomedicine carriers, such as controlling quality precisely, high reproducibility, fast and effective. Herein, this paper provides the brief introduction about the microfluidic technology and its application in the preparation of nanoparticulate drug carriers, which including polymer nanoparticles, lipid nanoparticles and hybrid nanoparticles. This review will provide ideas and references in utilization of microfluidic technology accurately and reasonably and also bring some prospects for its future development and challenges.
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Anti-tumor antibiotics exhibit great application potential in the anti-tumor therapy. Some drugs have become the first-line medication clinically. However, there are always various problems associated with anti-tumor antibiotics, such as poor solubility and instability as well as severe systemic side effects. It is important to choose suitable delivery carriers for a reasonable delivery system for a good targeting ability, enhanced anti-tumor efficacy and reduced adverse effects of the anti-tumor antibiotics, especially in the smart delivery systems. This review summarizes the carriers and the advances in the delivery systems of anti-tumor antibiotics, including anti-tumor antibiotic drugs currently on the market, in the clinical research stage and in the basic research stage.
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With the rapid development of nanotechnology,nanomaterials have received more and more attention in the application of medical transformation researches.As a new type of multifunctional inorganic nanomaterial with particle size between 1 to 100 nm,zinc oxide nanoparticles not only has common nano-effects including high specific surface area,quantum size and macroscopic tunneling,but also has some important special effects in optical,catalytic and biological aspects showing a wide range of application prospects.In recent years,with the deepening of the physicochemical properties and special effects of zinc oxide nanoparticles,its application in biomedical fields has gradually become a research hotspot in the field of biomedicine,such as molecular fluorescence probe,antibacterial,biosensor,drug carrier,and photochemical therapy of tumor.In this paper,the special effects of zinc oxide nanoparticles on optical,catalytic and biological aspects were highlighted,and its research progress was reviewed in medical imaging applications such as molecular imaging localization,biosignal sensing and molecular recognition,drug carrier development and tumor therapy.Furthermore,the problems in the translational application of zinc oxide nanoparticles were discussed.
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Chitosan and its derivatives with good characteristics such as non-toxicity,good biocompatibility and degradability,mu-cosal adhesion and permeability promotion etc,have been widely researched and applied in the field of drug carriers. Based on the re-cently published papers at home and abroad,the application and action mechanism of chitosan and its derivatives as drug carriers were analyzed and discussed,and the application and research progress of chitosan and its derivatives as anti-tumor drug targeting carriers, sustained-release and controlled-release drug carriers,ophthalmic drug carriers,gene carriers and gel bases were reviewed.
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Paclitaxel (PTX)-loaded self-assembling nano-micelles (PTX/NMs) were prepared based on amphiphilic cholesterol-bearing γ-polyglutamic acid (γ-PGA-graft-CH). The properties of PTX/NMs and were investigated. The results indicated that PTX could be entrapped in -PGA-graft-CH NMs. PTX/NMs was characterized with a size of (343.5 ± 7.3) nm, drug loading content of 26.9% ± 0.8% and entrapment efficiency of 88.6% ± 1.7% at the optimized drug/carrier ratio of 1/10, and showed a pH-sensitive sustainable drug-release and less cytotoxicity . release and the pharmacokinetics study in mice showed that the elimination half-life ( ) and area under curve (AUC) of PTX/NMs were significantly higher than those of PTX/polyoxyethylene castor oil (PTX/PCO), and less clearance (CL) of PTX/NMs was also observed. PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a good tumor-inhibiting activity in tumor-bearing mice. This study would lay a foundation on the potential application of -PGA-graft-CH NMs were the antitumor drug-delivery.
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As one of drug or gene carriers, peptide-modified pH-sensitive liposomes can actively target the tumor tissues, release anti-tumor drugs in specific areas, reduce side effects of drugs, and improve their therapeutic potency. In this review, the modification methods of peptide-modified liposomes and their anti-tumor applications by gene transfection and drug delivery are introduced. This paper is expected to provide a reference for the preparation of peptide-modified pH-sensitive liposomes and design of carriers for anti-tumor drugs.
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@#Functionalized graphene oxide is prepared based on graphene. It has attracted great interest from all over the world due to its good solubility, biocompatibility, high loading rate, and easy modification. This paper summarizes the surface modification of graphene oxide, and its applications on anti-tumor, antibacteria, anti-hypertension, gene therapy and biosafety as a drug carrier, providing new methods and ideas in the biomedical field.
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As a new carrier of intercellular information, the exosomes is widely regarded as a natural drug carrier for its extensive distribution, non-immunity and targeting in human body. Chinese herbal drugs act at multiple targets and through different pathways in the prevention and treatment of diseases, but the preparation is relatively simple, there is a low solubility in the effective ingredients and low bioavailability, which limit the efficacy of the medicine. Using the new drug delivery approach of the exosomes, it is better to deliver the effective components to target cells. In this review, we reviewed the biological characteristics of exosomes and its application as a carrier of Chinese herbal drugs.
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In this study, the endocytosis pathway of heparosan and its intracellular distribution were investigated in MCF-7 tumor cells and COS7 normal cells. The endocytosis inhibition and cellular probe location experiments showed that MCF-7 tumor cells took heparosan more efficiently and selectively than COS7 cells. The cellular uptake of heparosan was energy-dependent in both MCF-7 tumor cells and COS7 normal cells. Moreover, the major endocytosis pathway of heparosan into MCF-7 tumor cells was caveolin-mediated endocytosis and macropinocytosis. The internalized heparosan was mainly located in lysosomes of the cells.
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The development of pharmaceuticals has been providing many kinds of novel drug delivery systems, which are important for improving therapeutic effect and one of the most important fields in pharmaceutics. According to their application, we can generally divide the novel drug delivery systems into three categories:quickly performed drug delivery system, long-term drug delivery system and high effective drug delivery system. Some diseases, such as asthma, angina pectoris and migraine, require therapeutics urgently, and the drugs have to be absorbed in several minutes. Therefore, quickly performed drug delivery systems are developed, such as oral disintegrating tablets and nasal spray. For normal tablets and capsules, especially the drugs with short blood half life, the drug concentration in blood shows obvious peak-valley phenomenon, which reduces the therapeutic effect and requires multiple administration. To solve this problem, sustained drug release system was developed, which could release the drugs slowly and sustainably even in zero-order kinetics. The pulse drug delivery system was developed that can delayed and pulsed release drug for one or several times. This system is especially useful in the management of asthma and heart disease, which are often found in midnight or early morning when patients are in bed. Transdermal drug delivery system could release drugs sustainably and deliver the drugs through skin to blood circulation, providing long term activity. The water-insoluble drugs are difficult for pharmaceutical development, thus many methods were developed to improve the solubility and bioavailability of drugs. Although biopharmaceuticals are important for disease treatment, the application shadows by the poor stability and low bioavailability. Thus the biopharmaceutical delivery system was developed, which mainly focused on structure modification and encapsulation by carriers. Considering therapeutic effect requires interaction between drugs and their targets, it is important to deliver drugs to their targets. Therefore, targeting delivery systems were developed, which mainly based on the nanoparticles. Furthermore, on-demand release drug delivery systems are also developed with the property of environment-triggered drug release. In conclusion, the novel drug delivery systems were reviewed in this study.
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ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.
Subject(s)
Solubility , Flurbiprofen/analysis , Dissolution , Tablets/classification , Pharmaceutical PreparationsABSTRACT
This study was performed in order to creation of a doxorubicin conjugate with methacrylic acid (co)polymers for targeted tumor therapy. Poly(t-butylmethacrylate) with the optimal for biocompatible polymers molecular-weight characteristics (Mn= 12,400; Mw/Mn = 1.35) was synthesized by radical polymerization in the presence of thioglycolic acid as a chain transfer agent. The obtained polymer was converted by acid hydrolysis into a water-soluble copolymer of t-butylmethacrylate and methacrylic acid of 20:80 mass%, respectively. The copolymer of t-butylmethacrylate and methacrylic acid was modified with folic acid which has affinity for tumor cells. A conjugate of the copolymer with doxorubicin and also a conjugate with the folate vector were synthesized. Their formation was proved using elemental analysis and IR, UV, NMR spectroscopy. Thus, in the course of the study the conjugate of doxorubicin was synthesized, combining the drug and a vector for delivery of the drug. This compound is a promising, as it represents a new form of transport delivering a well-known and widely used anticancer agent doxorubicin.
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@#Asialoglycoprotein receptor(ASGPR)is a receptor expressed mainly on the surface of liver sinusoidal and basolateral cells. It can exclusively identity, combine and clear desialylated glycoproteins with exposed non-reducing D-galactose(Gal)or nacetylgalactosamine(GalNAc)as end groups. Based on this characteristic, ASGPR-mediated targeted liver cancer therapy has drawn extensive attention. The present review details the latest research progress of this field in three aspects, glycosylated prodrug, small molecular nanocarriers, and glycosylated gene complex therapy system.
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Most of the anticancer drugs have some limitations in clinical application,such as poor solubility,low targeting and cytotoxicity to normal tissue and organ.The application of drug carriers offers a solution of these problems to a certain extent.In recent years,some materials such as polymers,liposomes,carbon nanotubes (CNTs) were used as carriers of anticancer drugs.The utilization of these carriers improved drug targeting and reduced adverse reactions by targeted modification of carriers which ensured the slow release of the drugs and maintained the plasma concentration.In these carriers,CNTs,as a novel nano-material,have attracted more attention in nanomedical applications.CNTs not only possess nanoscaled diameter,hollow structure and large aspect ratio,resulting in large drug capacity,but also can selectively absorb near infrared lights and transform them into thermal energy,according to the research finding.The functionalized drug-loaded CNTs in combination with thermotherapy shows potential,which is expected to become a new targeting therapy of cancer.In this paper,the basic structure of CNTs,the application of CNTs as drug carriers,and the recent development of functionalized CNTs as drug carriers combined with thermotherapy in tumor therapy were summarized.
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@#In recent years, erythrocyte-inspired delivery systems have gained much attention. Erythrocytes(red blood cells, RBCs)are natural components of our bodies. Compared to the conventional drug delivery systems, RBCs have such advantages, as higher degree of biocompatibility and longer half-life. Herein, characteristics for drug delivery, preparation methods and recent research of RBC carriers are reviewed. Besides the latest development on RBC membrane-camouflaged nanoparticle systems(RBC-NP)and RBC membrane nanosponges, which have emerged as new trends of erythrocyte-inspired delivery systems are introduced.