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| 1 | Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes:current perspectives and future challenges显示文摘Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed. | Dinh Ha Ningning Yang Venkatareddy Nadithe | 2016 | Acta Pharmaceutica Sinica B2016，6，4： | 104 |
| 2 | Protein trans-splicing based dual-vector delivery of the coagulation factor Ⅷ gene显示文摘A dual-vector system was explored for the delivery of the coagulation factor VIII gene,using intein-mediated protein trans-splicing as a means to produce intact functional factor VIII post-translationally.A pair of eukaryotic expression vectors,expressing Ssp DnaB intein-fused heavy and light chain genes of B-domain deleted factor VIII (BDD-FVIII),was constructed.With transient co-transfection of the two vectors into 293 and COS-7 cells,the culture supernatants contained (137±23) and (109±22) ng mL–1 spliced BDD-FVIII antigen with an activity of (1.05±0.16) and (0.79±0.23) IU mL–1 for 293 and COS-7 cells,respectively.The spliced BDD-FVIII was also detected in supernatants from a mixture of cells transfected with inteinfused heavy and light chain genes.The spliced BDD-FVIII protein bands from cell lysates were visualized by Western blotting.The data demonstrated that intein could be used to transfer the split factor VIII gene and provided valuable information on factor VIII gene delivery by dual-adeno-associated virus in hemophilia A gene therapy. | ZHU FuXiang,LIU ZeLong,CHI XiaoYan & QU HuiGe Life Science College of Ludong University,Yantai 264025,China | 2010 | Science China(Life Sciences)2010，53，6： | 27 |
| 3 | siRNA therapeutics:a clinical reality显示文摘Since the revolutionary discovery of RNA interference(RNAi),a remarkable progress has been achieved in understanding and harnessing gene silencing mechanism;especially in small interfering RNA(siRNA)therapeutics.Despite its tremendous potential benefits,major challenges in most siRNA therapeutics remains unchanged-safe,efficient and target oriented delivery of siRNA.Twenty years after the discovery of RNAi,siRNA therapeutics finally charts its way into clinics.As we journey through the decades,we reminisce the history of siRNA discovery and its application in a myriad of disease treatments.Herein,we highlight the breakthroughs in si RNA therapeutics,with special feature on the first FDA approved RNAi therapeutics Onpattro(Patisiran)and the consideration of effective siRNA delivery system focusing on current siRNA nanocarrier in clinical trials.Lastly,we present some challenges and multiple barriers that are yet to be fully overcome in siRNA therapeutics. | Phei Er Saw Er-Wei Song | 2020 | Science China(Life Sciences)2020，63，4： | 26 |
| 4 | Progress and perspectives on targeting nanoparticles for brain drug delivery显示文摘Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed. | Huile Gao | 2016 | Acta Pharmaceutica Sinica B2016，6，4： | 26 |
| 5 | Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application显示文摘Erythrocytes(red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems(DDS) because of their features of biocompatibility,biodegradability, and long circulating half-life. Accordingly, a 'camouflage' comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed,providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems. | Qing Xia Yongtai Zhang Zhe Li Xuefeng Hou Nianping Feng | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 26 |
| 6 | Adapting liposomes for oral drug delivery显示文摘Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes,oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract,difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes. | Haisheng He Yi Lu Jianping Qi Quangang Zhu Zhongjian Chen Wei Wu | 2019 | Acta Pharmaceutica Sinica B2019，9，1： | 23 |
| 7 | Recent advances of microneedles for biomedical applications: drug delivery and beyond显示文摘The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing(3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications. | Jian Yang Xinli Liu Yunzhi Fu Yujun Song | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 21 |
| 8 | A Review on Graphene-Based Nanomaterials in Biomedical Applications and Risks in Environment and Health显示文摘Graphene-based nanomaterials(GBNs) have attracted increasing interests of the scientific community due to their unique physicochemical properties and their applications in biotechnology, biomedicine, bioengineering, disease diagnosis and therapy. Although a large amount of researches have been conducted on these novel nanomaterials, limited comprehensive reviews are published on their biomedical applications and potential environmental and human health effects. The present research aimed at addressing this knowledge gap by examining and discussing:(1) the history, synthesis,structural properties and recent developments of GBNs for biomedical applications;(2) GBNs uses as therapeutics,drug/gene delivery and antibacterial materials;(3) GBNs applications in tissue engineering and in research as biosensors and bioimaging materials; and(4) GBNs potential environmental effects and human health risks. It also discussed the perspectives and challenges associated with the biomedical applications of GBNs. | Thabitha P.Dasari Shareena Danielle McShan Asok K.Dasmahapatra Paul B.Tchounwou | 2018 | Nano-Micro Letters2018，10，3： | 18 |
| 9 | Treatment of diabetic retinopathy: Recent advances and unresolved challenges显示文摘Diabetic retinopathy(DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor(VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema(DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation(PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. | Michael W Stewart | 2016 | World Journal of Diabetes2016，7，16： | 18 |
| 10 | Nano-formulations for transdermal drug delivery:A review显示文摘Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nanoformulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations(vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed. | Xingli Zhou Ying Hao Liping Yuan Sushmita Pradhan Krista Shrestha Ojaswi Pradhan Hongjie Liu Wei Li | 2018 | Chinese Chemical Letters2018，29，12： | 17 |
| 11 | Role of nitric oxide in hepatic ischemia-reperfusion injury显示文摘Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO. | Arunotai Siriussawakul Ahmed Zaky John D Lang | 2010 | World Journal of Gastroenterology2010，16，48： | 14 |
| 12 | Injected nanocrystals for targeted drug delivery显示文摘Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system(MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e.,top-down and bottom-up technologies. | Yi Lu Ye Li Wei Wu | 2016 | Acta Pharmaceutica Sinica B2016，6，2： | 14 |
| 13 | Mesalazine preparations for the treatment of ulcerative colitis: Are all created equal?显示文摘Oral mesalazine(also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate ulcerative colitis, with high rates of efficacy in induction and maintenance of remission.The therapeutic effect of mesalazine occurs topically at the site of diseased colonic mucosa. A myriad of oral mesalazine preparations have been formulated with various drug delivery methods to minimize systemic absorption and maximise drug availability at the inflamed colonic epithelium. It remains unclear whether different oral mesalazine formulations are bioequivalent. This review aims to evaluate the differences between mesalazine formulations based on the currently available literature and explore factors which may influence the selection of one agent above another. | Bei Ye Daniel R van Langenberg | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 14 |
| 14 | Effect of prolonged second stage of labor on maternal and neonatal outcomes显示文摘Objective:To discuss the effect of prolonged second stage of labor on maternal and neonatal outcomes.Methods:A total of 101 primiparas with the length of second stage of labor longer than 2 h were selected and pregnant women with the length less than 2 h served as control.The maternal and neonatal outcomes of two groups were observed and compared.Results:A total of 62.1%(18/11) with the length of second stage of labor between 120 min and 180 min,46.7%(28/32) between 181 min and 240 min and 12 longer than 241 min underwent vaginal delivery.The longer the length of second stage of labor,the lower score of Apgar scale for infants in 1 min,and the higher the incidence of asphyxia.But there was no difference in scale in 5 min.As second stage of labor prolonged,the incidences of cesarean section and of postpartum hemorrhage increased. Conclusions:Almost half of puerperas with the length of second stage of labor longer than 2 h underwent vaginal delivery.The prolonged second stage of labor can decrease the score of Apgar scale in 1 min,increase the incidence of asphyxia,but has no effect on scale in 5 min.It still need more evidence from evidence medicine to definition of time and treatment of second stage of labor. | Wei-hong Li Hong-yu Zhang Yi Ling SongJin | 2011 | Asian Pacific Journal of Tropical Medicine2011，4，5： | 13 |
| 15 | Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy显示文摘Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy(RT). However, there is no effective drug delivery system to effectively overcome the blood–brain barrier(BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles(ch-Kn(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1(LRP1) that is overexpressed on brain capillary endothelial cells(BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2(MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-Kn(s-s)R8-An micelles maintained a reasonable size(80–160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration(CMC) with positive surface charge, ranging from 15 to40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency in vitro, improved uptake in glioma cells and good biocompatibility in vitro and in vivo. In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells in vitro. Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells. | Xiuxiu Jiao Yuan Yu Jianxia Meng Mei He Charles Jian Zhang Wenqian Geng Baoyue Ding Zhuo Wang Xueying Ding | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 13 |
| 16 | ROS-responsive drug delivery systems for biomedical applications显示文摘In the field of biomedicine, stimuli-responsive drug delivery systems(DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species(ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes,whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore,ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field. | Wenhui Tao Zhonggui He | 2018 | Asian Journal of Pharmaceutical Sciences2018，13，2： | 12 |
| 17 | Two-dimensional nanomaterials: fascinating materials in biomedical field显示文摘Due to their high anisotropy and chemical functions,two-dimensional(2D)nanomaterials have attracted increasing interest and attention from various scientific fields,including functional electronics,catalysis,supercapacitors,batteries and energy materials.In the biomedical field,2D nanomaterials have made significant contributions to the field of nanomedicine,especially in drug/gene delivery systems,multimodal imaging,biosensing,antimicrobial agents and tissue engineering.2D nanomaterials such as graphene/graphene oxide(GO)/reduced graphene oxide(r GO),silicate clays,layered double hydroxides(LDHs),transition metal dichalcogenides(TMDs),transition metal oxides(TMOs),black phosphorus(BP),graphitic carbon nitride(g-C3N4),hexagonal boron nitride(h-BN),antimonene(AM),boron nanosheets(B NSs)and tin telluride nanosheets(Sn Te NSs)possess excellent physical,chemical,optical and biological properties due to their uniform shapes,high surface-to-volume ratios and surface charge.In this review,we first introduce the properties,structures and synthetic strategies of different configurations of 2D nanomaterials.Recent advances and paradigms of 2D nanomaterials in a variety of biomedical applications,ranging from drug delivery,cancer treatment,bioimaging and tissue engineering to biosensing are discussed afterwards.In the final part,we foresee the development prospects and challenges of 2D nanomaterials after summarizing the research status of ultrathin 2D nanomaterials. | Tingting Hu Xuan Mei Yingjie Wang Xisheng Weng Ruizheng Liang Min Wei | 2019 | Science Bulletin2019，64，22： | 12 |
| 18 | New-generation biomedical materials:Peptide dendrimers and their application in biomedicine显示文摘Peptide dendrimers are attractive synthetic polymers and have been widely used as a new generation of biomaterials in recent years.Peptide dendrimers,as well as general dendrimers,may be synthesized to reach nano sizes,and display well-defined architectures,highly-branched structures,high density of functional terminal groups,and controllable molecular weights.On the other hand,peptide dendrimers have properties similar to proteins and some special characteristics,such as good biocompatibility,water solubility and resistance to proteolytic digestion.Due to these advantages,peptide dendrimers have received considerable attention in biomedicine.This review focuses on the development of peptide dendrimers with emphasis on their applications both in diagnostics and in therapy. | GU ZhongWei,LUO Kui,SHE WenChuan,WU Yao & HE Bin National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China | 2010 | Science China Chemistry2010，53，3： | 12 |
| 19 | Challenges to the early diagnosis and treatment of breast cancer in developing countries显示文摘This critical review of the literature assembles and compares available data on breast cancer clinical stage, time intervals to care, and access barriers in different countries. It provides evidence that while more than 70% of breast cancer patients in most high-income countries are diagnosed in stages Ⅰ and Ⅱ, only 20%-50% patients in the majority of low- and middleincome countries are diagnosed in these earlier stages. Most studies in the developed world show an association between an advanced clinical stage of breast cancer and delays greater than three months between symptom discovery and treatment start. The evidence assembled in this review shows that the median of this interval is 30-48 d in high-income countries but 3-8 mo in low- and middle-income countries. The longest delays occur between the first medical consultation and the beginning of treatment, known as the provider interval. The little available evidence suggests that access barriers and quality deficiencies in cancer care are determinants of provider delay in low- and middle-income countries. Research on specific access barriers and deficiencies in quality of care for the early diagnosis and treatment of breast cancer is practically non-existentin these countries, where it is the most needed for the design of cost-effective public policies that strengthen health systems to tackle this expensive and deadly disease. | Karla Unger-Salda?a | 2014 | World Journal of Clinical Oncology2014，5，3： | 12 |
| 20 | Deworming of stray dogs and wild canines with praziquantel-laced baits delivered by an unmanned aerial vehicle in areas highly endemic for echinococcosis in China显示文摘Background:Canines,the definitive hosts for the parasites causing alveolar(AE)and cystic echinococcosis(CE),are the main source of this infections playing the key role in the transmission.The ten-year mortality rate of AE is extremely high(94%)if the patients are not given sustained treatment.The aim of this field study is to explore the possibility of delivery of praziquantel-laced baits using unmanned aerial vehicles(UAVs)aimed at deworming wild canines in the endemic areas.Methods:UAVs were compared to manual bait delivery in the 1-km^(2)test areas followed by testing of canine faeces using an Echinococcus coproantigen ELISA test in the ensuing year.The outcomes of the two approaches were compared with respect to time of delivery and overall cost.Findings:Compared to manual bait delivery,delivery by UAVs saved up to 67%of the overall cost.Three times more staff was needed for the former approach compared to the latter and,time wise,UAV bait delivery saved 350%compared to manual bait delivery on average.With regard to investment needed,the use of UAVs showed an efficiency 2.5 times better than manual bait delivery.Compared to the area served by UAVs,the average positive rate for the canine faecal samples was more than 38%higher in the area served manually.Conclusion:The technique of bait delivery with praziquantel using UAVs for canine deworming has a strong potential with regard to savings of manpower,time and overall cost in areas highly endemic for echinococcosis. | Qing Yu Ning Xiao Shi-jie Yang Shuai Han | 2017 | Infectious Diseases of Poverty2017，6，1： | 12 |
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