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51.
52.
【摘要】目的:构建angiopep-2与转铁蛋白共修饰脂质体,并对其理化性质和跨血脑屏障能力进行评价。方法 采用薄膜分散法制备转铁蛋白(TF)与angiopep-2共修饰载脂质体(ANG/TF-LPs),考察其粒径,电位,血清稳定性等理化特征。通过定量细胞摄取实验考察脑内皮bEnd.3细胞对ANG/TF-LPs的摄取效率。构建血脑屏障体外模型,考察不同脂质体的跨血脑屏障能力。结果 所制备的ANG/TF-LPs粒径为93±13.5 nm, Zeta 电位为7.55±1.85 mV。在24 h内具有良好的血清稳定性。体外细胞摄取实验表明,bEnd.3细胞对ANG/TF-LPs的摄取效率分别是TF-LPs、ANG-LPs和LPs的2.9倍、2.4倍和4.8倍,差异具有统计学意义(P<0.01);ANG/TF-LPs的跨血脑屏障效率分别是TF-LPs、ANG-LPs和LPs的3.1倍、2.9倍和6.8倍,差异具有统计学意义(P<0.01)。结论 ANG/TF-LPs制备工艺简单,经过angiopep-2与转铁蛋白修饰后,脂质体的跨血脑屏障能力显著增强,是一种潜在高效的脑部靶向给药系统。 相似文献
53.
The X-linked deubiquitinase USP9X affects the stability and activity of numerous regulatory proteins that influence cell survival. Recent studies suggest that decreased USP9X expression can confer a selective advantage onto developing cancer cells and thereby promotes disease progression. To examine the effect of USP9X on the cellular responses to anticancer therapies, we derived cancer cell lines in which the USP9X locus was disrupted by homologous recombination. The resulting USP9X-deficient cancer cells exhibited increased activation of apoptotic pathways and markedly decreased clonogenic survival in response to 5-fluorouracil, a chemotherapeutic drug that is widely used for treatment of gastrointestinal malignancies. These unexpected results suggest that cancers with low USP9X expression might be specifically sensitized to some conventional therapeutic agents. 相似文献
54.
5种TNFα单抗及其类似物的TNFα杀伤抑制活性的比较 总被引:1,自引:0,他引:1
目的:比较5种以TNFα为治疗靶位的治疗性单抗及其类似物的TNFα杀伤抑制活性。方法:以Anti-TNFαrhmMcAb为参比品,采用TNFα杀伤抑制法测定其他4种制品的TNFα杀伤抑制活性,剂量-反应曲线进行四参数拟合后,测定抑制1.0 ng·mL-1TNFα杀伤的半数有效浓度(EC50)。以Anti-TNFαrhmMcAb的EC50值除以待测样品EC50值计算样品的相对活性。结果:相对于Anti-TNFαrhmMcAb,TNFαⅡR-Fc、Anti-TNFαrhuMcAb、Anti-TNFαsrhmMcAb和Anti-TNFαarhuM-cAb的TNFα杀伤抑制活性分别为4860%,248%,505%,90%。结论:TNFα杀伤抑制方法可以快速测定治疗性抗TNFα单抗及其类似物的TNFα杀伤抑制活性,不同制品的测定结果之间具有一定可比性,可以根据测定结果对不同制品的生物学活性进行评价和比较。 相似文献
55.
Shilpee Das Jagruti L. Desai Hetal P. Thakkar 《Indian journal of pharmaceutical sciences》2013,75(6):707-715
The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride. 相似文献
56.
《Journal of microencapsulation》2013,30(7):701-708
AbstractNovel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients. 相似文献
57.
Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~ 500 μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures. 相似文献
58.
《Expert opinion on biological therapy》2013,13(5):683-696
Adenoviral cancer gene therapy approaches have resulted in promising recent results. Following only a decade of intense development, some of the crucial obstacles are now being overcome. Insufficient transduction has been the main limitation of earlier approaches. A new approach for increasing transduction of tumour cells is utilisation of replication-competent oncolytic agents, such as conditionally replicating adenoviruses (CRADs). The anti-tumour effect is caused by replication of the virus per se and, thus, replication must be restricted to tumour cells to protect normal tissues from damage. Tissue-specific promoters (TSPs) represent a powerful tool for decreasing the toxicity of cancer gene therapy to normal tissues and have previously been utilised for specific mutation compensation or delivery of prodrug-converting enzymes. However, TSPs can also be used for controlling crucial viral replication regulators and consequent restriction of replication to tumour cells. Initial clinical trials have demonstrated the safety and suggested efficacy for TSP-controlled CRADs as a novel approach for cancer gene therapy. 相似文献
59.
《Expert opinion on biological therapy》2013,13(6):605-617
Understanding the role of the epidermal growth factor receptor (EGFR) in cellular signalling processes underlying malignancy has enabled the development of rationally designed EGFR-targeted therapeutics. Strategies have been devised to interfere with the EGFR signalling at three different levels: at the extracellular level, competing with ligand binding; at the intracellular level, inhibiting the activation of the tyrosine kinase; or at the mRNA level, modulating the expression of the EGFR protein. Each of these strategies has proven to have an antitumour effect mediated by events such as inhibition of cell proliferation, induction of apoptosis, decrease of cellular invasion and migration; and/or inhibition of angiogenesis. Furthermore, the combination of these strategies with traditional chemotherapy or radiotherapy has generally resulted in enhanced antitumour effects. Likewise, the benefit of interfering simultaneously with different signalling pathways has been documented to improve tumour growth inhibition. These preclinical results have encouraged clinical studies that led to the FDA approval of three drugs. However, finding the perfect strategy for each individual patient appears to be a limiting factor, demanding further research to be able to generate relevant molecular expression profiles on a case-to-case basis. Taken together, a successful EGFR inhibition will require a better understanding of signalling pathways in combination with the development of rationally designed effective molecules. 相似文献
60.
《Expert opinion on biological therapy》2013,13(5):765-771
Bacterial ghosts are empty cell envelopes originating from Gram-negative bacteria. They have a natural outer surface make-up which provides them with the original targeting functions of the bacteria they are derived from and are thus able to bind to and/or are taken up by specific cells or tissues of animal, human or plant origin. The extended bacterial ghost system represents a platform technology for creating new qualities in non-living carriers which can be used for the specific targeting of drugs, DNA or other compounds to overcome toxic or non-desired obstacles. Freeze dried bacterial ghosts are stable without the requirement of a cold chain and can be effectively administered orally and aerogenically as drug carriers. The new system is an alternative to liposomes and may have an advantage due to its higher specificity for targeting specific tissues, its easy method of production and its versatility in entrapping and packaging various compounds in different compartments of the carriers. 相似文献