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1.
Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery 总被引:1,自引:0,他引:1
Electrospun nanofibers with a high surface area to volume ratio have received much attention because of their potential applications for biomedical devices, tissue engineering scaffolds, and drug delivery carriers. In order to develop electrospun nanofibers as useful nanobiomaterials, surfaces of electrospun nanofibers have been chemically functionalized for achieving sustained delivery through physical adsorption of diverse bioactive molecules. Surface modification of nanofibers includes plasma treatment, wet chemical method, surface graft polymerization, and co-electrospinning of surface active agents and polymers. A variety of bioactive molecules including anti-cancer drugs, enzymes, cytokines, and polysaccharides were entrapped within the interior or physically immobilized on the surface for controlled drug delivery. Surfaces of electrospun nanofibers were also chemically modified with immobilizing cell specific bioactive ligands to enhance cell adhesion, proliferation, and differentiation by mimicking morphology and biological functions of extracellular matrix. This review summarizes surface modification strategies of electrospun polymeric nanofibers for controlled drug delivery and tissue engineering. 相似文献
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Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release. 相似文献
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《Asian Journal of Pharmaceutical Sciences》2018,13(5):459-471
The aim of this study was to elucidate the optimized fabrication factors influencing the formation and properties of shellac (SHL) nanofibers loaded with an antimicrobial monolaurin (ML). The main and interaction effects of formulation and process parameters including SHL content (35%–40% w/w), ML content (1%–3% w/w), applied voltage (9–27 kV) and flow rate (0.4–1.2 ml/h) on the characteristic of nanofibers were investigated through a total of 19 experiments based on a full factorial design with three replicated center points. As a result, the SHL content was the major parameter affecting fiber diameter. Another response result revealed that the SHL content would be also the most significant negative impact on amount of beads. An increase in the concentration of SHL leaded to a reduction in the amount of beads. From the results of characterization study, it was proved that ML might be entrapped between the chains of SHL during the electrospinning process exhibiting an excellent encapsulation. According to the response surface area, small (~488 nm) and beadless (~0.48) fibers were obtained with the SHL and ML contents of 37.5% and 1.1% w/w respectively, at the applied voltage of 18 kV and the flow rate of 0.8 ml/h. In addition, the results of the kill-kinetic studies showed that SHL nanofibers loaded with ML exhibited an excellent antibacterial activity against Staphylococcus aureus, while Escherichia coli was less affected due to the hydrophilic structure of the its outer membrane. ML also exerted an antifungal activity by reducing the number of Candida albicans colonies. Based on their structural and antimicrobial properties, SHL nanofibers containing ML could be potentially used as a medicated dressing for wound treatment. 相似文献
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目的 观察不同质量比聚乳酸-羟基乙酸(PLGA)胆总管支架在体外胆汁中降解情况,实验探索可降解支架修复胆道损伤的可行性.方法 用扫描电镜观察不同质量比的PLGA纳米纤维膜微观形貌,并测定其短期体外胆汁中降解率.观察其在胆总管Ⅰ期缝合、胆总管切开置入支架和胆管缺损修补手术中的作用.术后观察动物黄疽和胆漏情况和动物自身术前和术后肝酶(ALT、AST、ALP)和血胆红素的变化.进行Masson染色和平滑肌肌动蛋白(α-SMA)、增殖细胞核抗原(PCNA)免疫组化观察肝脏及胆管损伤部位组织病理学改变.结果 PLGA 75/25和90/10两种比例的纤维在胆汁中没有发生明显的降解和变形.胆管缺损修补手术的猪胶原增生程度轻,排列相对有序,α-SMA免疫组化评分最低,PCNA免疫组化示胆管缺损区域有新生胆管上皮细胞形成.结论 可降解静电纺丝PLGA纳米纤维支架能有效支撑和修复胆管缺损. 相似文献
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Controlled green tea polyphenols release from electrospun PCL/MWCNTs composite nanofibers 总被引:1,自引:0,他引:1
Shao S Li L Yang G Li J Luo C Gong T Zhou S 《International journal of pharmaceutics》2011,421(2):310-320
Poly(?-caprolactone)/multi-walled carbon nanotubes (PCL/MWCNTs) composite nanofibers with various content of green tea polyphenols (GTP) were successfully fabricated via an electrospinning technology to maintain the chemical structural stability of GTP. The non-covalent interaction between MWCNTs and GTP was measured by UV-vis spectrophotometer and FT-IR. The topographical features of the nanofibers were characterized by scanning electron microscopy (SEM). The dispersibility of MWCNTs and the distribution of GTP in nanofibers were observed by transmission electron microscopy (TEM) and laser scanning confocal microscope (LSCM), respectively. In vitro degradation was also characterized in terms of the morphological change and the mass loss of the nanofiber meshes. In vitro GTP release behavior was investigated in phosphate-buffered solution (PBS) at 37°C. Alamar blue assays were performed to estimate the cytotoxicity of the nanofibers with normal osteoblast cells and the antiproliferative effects to A549 and Hep G2 tumor cells. The results exhibited that the GTP-loaded composite nanofibers possessed a significant inhibition effect to tumor cells. Therefore, GTP, as a multifunctional drug, encapsulated into polymer composite nanofibers, must have broad application prospects in cancer therapy. 相似文献
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Acute injuries or wound is required the fast delivery of drug to control infections without any side effect. In this direction in the present investigation, antibiotic ciprofloxacin loaded hydrophilic biodegradable poly vinyl alcohol (PVA) and sodium alginate (NaAlg) electrospun composite nanofiber based transdermal patch was developed for local delivery of antibiotic drug. The antibiotic drug ciprofloxacin was loaded in it by active loading. The drug entrapped in the composite nanofibers was confirmed by the scanning electron microscopy and swelling behavior. The in vivo studies were carried on male rabbits by using the drug loaded and unloaded composite nanofibers transdermal patch and marketed one. It is observed that, in vitro activity provides a sustained and controlled release pattern of the drug from transdermal patch. The mechanism of drug release was also studied using different models. The nanofiber transdermal patch follows the Higuchi and Korsmeyer–Peppas model for drug release. The in vivo studies demonstrate that, wound healing takes place in less time as compared drug unloaded patch. Hydroxyproline produced in wound bed with time shows that it content is maximum in case drug loaded PAV-NaAlg patch. This demonstrates that wound healing rate is higher in case drug loaded PVA-NaAlg transdermal patch. 相似文献
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The purpose of this study was to evaluate both in vitro and in vivo anticancer activities against colorectal cancer (CRC) of electrospun polylactide (PLA) nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation, the drug-loaded fiber mats were locally implanted into mouse colorectal CT26 tumor-bearing mice, followed with histological analysis and detection of survival rate. The results showed that the drug-loaded fiber mats was similar to that of the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much superior to intravenous injection of free drug in vivo anticancer activities, presenting with suppressed tumor growth rate and prolonged survival time of mice. In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be significantly improved by using PLA electrospun nanofibers as local drug delivery system. 相似文献
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Xuening Chen Xiaoling Fu Jian-gang Shi Hongjun Wang 《Nanomedicine : nanotechnology, biology, and medicine》2013,9(8):1283-1292
Orientation of extracellular matrix (ECM) fibrils contributes to the anisotropy of bones, but little is known about how fibril orientation induces osteoblastic responses. Here, biomimetic polycaprolactone/type I collagen (PCL/COL-1) nanofibers with aligned and random fiber arrangements were used as models to study their effects on pre-osteoblasts. Elongated cell morphology, accelerated cell migration, elevated alkaline phosphatase activity and calcium content, up-regulated expression of osteogenic markers and differential expression of integrins were observed for cells cultured on two-dimensional (2D) aligned nanofibers. To emulate in vivo tissue structure, three-dimensional (3D) cell/nanofiber constructs with cells embedded among nanofiber layers were built via layer-by-layer assembly. These showed that aligned nanofibers in the 3D constructs continuously induced cell polarization and promoted osteogenesis. These findings revealed that nanofiber alignment favored osteogenic differentiation of pre-osteoblasts, and demonstrated the potential of 3D cell/nanofiber construct as a model to study specific cell-material interactions in a physiologically relevant environment.From the Clinical EditorIn this novel study, biomimetic polycaprolactone/type I collagen nanofibers with aligned and random fiber arrangements were used to demonstrate their effects on pre-osteoblasts with an overall goal of improved orientation of extracellular matrix fibrils to optimize osteoblastic responses and improve osteogenesis for future therapeutic exploitation. 相似文献
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人体内存在各种各样的天然多肽,它们参与调控各种生理功能,在临床应用上具有非常重要的开发价值。目前全球药物市场上有60~70个多肽药物,更多的多肽药物处在各级临床试验、临床前试验和实验室研究阶段。很多多肽药物以G蛋白偶联受体为靶点。传统的化学合成也仍然是开发多肽药物最主要的手段。然而,我们在多肽药物开发方面仍面临各种挑战,不仅要解决传统问题如不稳定,易降解,难穿越细胞膜,而且也要进一步降低生产成本,完善大批量生产工艺技术。尤其是多肽药物的口服生物利用度问题,一直是我们面临的最大的挑战和决定市场的关键因素。随着在现代技术及其它方面不断取得进展,多肽药物将具有更加广阔的前景。在新一代受体靶向药物研究中,多肽更被作为一种有效的药物载体,通过细胞表面受体将药物传递到特定细胞,达到提高特异性,减少副作用的目的。 相似文献
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The use of polymer-based electrospun nanofibers containing amorphous drug dispersions for the delivery of poorly water-soluble pharmaceuticals 总被引:2,自引:0,他引:2
Brewster ME Verreck G Chun I Rosenblatt J Mensch J Van Dijck A Noppe M Ariën A Bruining M Peeters J 《Die Pharmazie》2004,59(5):387-391
Electrostatic spinning was applied to the preparation of drug-laden nanofiber for potential use in oral and topical drug delivery. While this technique is in its infancy with regard to pharmaceutical applications, a number of recent publications suggest that it may be of high value in the formulation of poorly water-soluble drugs by combining nanotechnology and solid solution/dispersion methodologies. The purpose of this article is to describe some of these recently published applications. For immediate release oral application, a water-soluble cellulose polymer was selected (i.e., hydroxypropylmethylcellulose, HPMC) while for topical application, a nonbiodegradable, water-insoluble polymer was investigated (i.e., a segmented polyurethane, SPU). Solutions of the polymer and the drugs in appropriate solvents could be spun across various potentials (16-24 kV) generating nanofibers with diameters ranging from 300 to 2000 nm. Dissolution studies found that the non-woven fabrics derived from HPMC and containing itraconazole dissolved over a time course of minutes to hours depending on the formulation used as well as the drug/polymer ratios. Drug release from the SPU samples was dependent on the incorporated drug as well as nanostructure obtained. 相似文献
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Sehgal A 《Current opinion in drug discovery & development》2002,5(2):245-250
Peptides make up only a fraction of therapeutically beneficial pharmaceutical molecules that are either in clinical testing or in the market. Despite the initially low number and impact of peptides on therapeutics, their potential has just intensified with new developments in modifications, stability, delivery and preclinical success. With the completion of the human genome sequence and developments in the proteomics field, peptides are emerging as important molecules for cancer therapy. Several peptides with exciting preclinical results have now entered into clinical trial for the treatment of human cancers. In this review, some of the recent advances in peptide-based cancer therapeutics will be discussed. 相似文献
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Dijkgraaf I Boerman OC Oyen WJ Corstens FH Gotthardt M 《Anti-cancer agents in medicinal chemistry》2007,7(5):543-551
During the past decade, radiolabeled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for tumor diagnosis and therapy. The specific receptor binding property of the ligand can be exploited by labeling the ligand with a radionuclide and using the radiolabeled ligand as a vehicle to guide the radioactivity to the tissues expressing a particular receptor. The concept of using radiolabeled receptor binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. Receptor binding peptides labeled with gamma emitters ((123)I, (111)In, (99m)Tc) can visualize receptor-expressing tissues, a technique referred to as peptide-receptor radionuclide imaging (PRRI). In addition, labeled with beta emitters ((131)I, (90)Y, (188)Re, (177)Lu) these peptides have the potential to irradiate receptor-expressing tissues, an approach referred to as peptide-receptor radionuclide therapy (PRRT). The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and PRRT of neuroendocrine tumors. Other peptides such as Minigastrin, GLP-1, CCK, bombesin, substance P, neurotensin, and RGD peptides are currently under development or undergoing clinical trials. In this review, an overview of the criteria of peptide ligand development, the selection of radioisotopes, labeling methods, and chemical aspects of radiopeptide synthesis is given. In addition, the current state of clinical use of radiopeptides for diagnosis and therapy of tumors is discussed. 相似文献
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Gotthardt M Boermann OC Behr TM Béhé MP Oyen WJ 《Current pharmaceutical design》2004,10(24):2951-2963
Peptide-based radiopharmaceuticals have been introduced into clinical work more than a decade ago. The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and also receptor-mediated peptide-radiotherapy of neuroendocrine tumors. For in vivo use as radiopharmaceutical, the natural peptide is modified in order to enhance the metabolic stability and to allow stable labeling with a so-called residualizing label. This means, that a radiometal chelator complex bound to a modified peptide stable in serum is internalized into the target cells via a specific receptor. The peptide then undergoes lysosomal degradation leaving the radiometal-chelator complex trapped inside the cell, leading to a high target to background ratio. The successful development of new radiopeptides is thus dependent on modifications of a given natural peptide while preserving the binding affinity for the target receptor(s) at the same time. Other peptides than somatostatin are under development for use as radiopeptides such as Minigastrin, GLP-1, VIP, Substance P, or Neurotensin. Some show very favorable results in clinical trials, like Minigastrin for example. Furthermore, there is increasing interest in peptide-binding sites other than the "classical" receptors for regulatory peptides specifically over-expressed by (neuroendocrine) tumors. In this paper, we provide an overview of the biochemical and radiochemical aspects of radiopeptide development, the current state of clinical use of radiopeptides for diagnosis and therapy of tumors, the current state of development of new compounds, and future developments. 相似文献
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《Drug discovery today》2022,27(5):1367-1380
The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host. 相似文献
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Molecular imaging consists of non-invasive monitoring of spatial-temporal distribution of molecular or cellular processes, and may be used for early disease detection and real-time monitoring of therapeutic responses. Several strategies have been developed over the last two decades. Early attempts used monoclonal antibodies or antibody fragments and, although specific targeting was achieved, these probes was largely unsuccessful. In the quest for better agents, labeled peptides were then used. Peptides are easier to synthesize, less likely to be immunogenic, and have rapid blood clearance, which results in adequate target-to-background ratios in a short period of time. This review discusses state-of-the-art cancer imaging by means of labeled peptides, the radionuclide, optical and nanoplatform-based imaging techniques which can provide functional information of the disease and track biochemical processes in vivo. The advantages and disadvantages of each technique are discussed. Lastly, the emphasis of this paper is on the new multimodal probes which can overcome individual limitations and exploit the individual strengths of the latest molecular imaging techniques. 相似文献
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Banks WA 《Expert opinion on drug delivery》2006,3(6):707-712
Peptides hold great potential as CNS drugs, but their delivery to the CNS is problematic. However, actual roadblocks to peptide delivery are different from those often perceived. Many peptides cross the blood-brain barrier by saturable and non-saturable mechanisms, and accumulate in brain in amounts sufficient to produce physiological effects. Peripheral factors (e.g., short half-life in blood) can be dominant factors limiting therapeutic use. Production of therapeutics that are enzymatically resistant and have long circulation times, even when the blood-brain barrier penetration is low, can result in substances with significant CNS accumulation. Surprisingly low amounts of peptide in brain can result in CNS effects, and so the dose needed for brain delivery is generally much smaller than for peripheral tissues. Brain-to-blood transporters can greatly limit CNS accumulation of a potential therapeutic. Finally, intranasal and intrathecal routes may be especially useful for substances that are rapidly degraded in blood or are large and hydrophobic, respectively. 相似文献
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《Expert opinion on drug delivery》2013,10(6):707-712
Peptides hold great potential as CNS drugs, but their delivery to the CNS is problematic. However, actual roadblocks to peptide delivery are different from those often perceived. Many peptides cross the blood–brain barrier by saturable and non-saturable mechanisms, and accumulate in brain in amounts sufficient to produce physiological effects. Peripheral factors (e.g., short half-life in blood) can be dominant factors limiting therapeutic use. Production of therapeutics that are enzymatically resistant and have long circulation times, even when the blood–brain barrier penetration is low, can result in substances with significant CNS accumulation. Surprisingly low amounts of peptide in brain can result in CNS effects, and so the dose needed for brain delivery is generally much smaller than for peripheral tissues. Brain-to-blood transporters can greatly limit CNS accumulation of a potential therapeutic. Finally, intranasal and intrathecal routes may be especially useful for substances that are rapidly degraded in blood or are large and hydrophobic, respectively. 相似文献