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排序方式: 共有204条查询结果,搜索用时 46 毫秒
1.
Fattal E Roques B Puisieux F Blanco-Prieto MJ Couvreur P 《Advanced drug delivery reviews》1997,28(1):85-96
This paper reviews the preparation and characterization of small poly(lactic-co-glycolic acid) microspheres (mean size lower than 10 μm) containing small peptides and prepared by a water-in-oil-in-water emulsion solvent evaporation technique. These microspheres were shown to encapsulate very efficiently a 33 amino acid peptide (V3 BRU) and in vitro release kinetics studies showed that such microspheres could be employed for both oral vaccination and controlled release. The encapsulation of a seven amino acid peptide (pBC 264) led on the contrary to a very low encapsulation efficiency. In order to increase the encapsulation of pBC 264, two strategies were adopted: (i) taking into account the solubility of pBC 264 at different pH, the inner aqueous phase was maintained at a basic pH where the peptide was soluble, while the external aqueous phase was acidic; (ii) ovalbumin was added to stabilize the inner emulsion. These two strategies allowed us to increase significantly the encapsulation rate of pBC 264. Nevertheless, the in vitro release kinetics of the peptide were strongly influenced by the presence of ovalbumin which seems to form pores in the microsphere structure. By contrast, when ovalbumin was replaced by Pluronic(R) F68, microspheres did not have pores, thus the release profile and the extent of the burst were much smaller. When microspheres were stereotactically implanted in the rat brain, in vivo release profiles were in good agreement with the release observed in vitro. In conclusion, these microspheres are well suited for the slow delivery of neuropeptides in the brain, a feature expected to facilitate the study of long term effects of these compounds. 相似文献
2.
Nakada Yuichiro Fattal Elias Foulquier Monique Couvreur Patrick 《Pharmaceutical research》1996,13(1):38-43
Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate 33P-pdT16 loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT16 Results. Organ distribution study has shown that nanoparticles deliver 33P-pdT16 specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT16 against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver. 相似文献
3.
The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems. 相似文献
4.
BACKGROUND: It is known that exertion can aggravate migraine headache. However, the relationship between exertion and migraine aura is unknown. OBJECTIVE: To study the relationship between exertion and migraine aura. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: A 67-year-old man presented with recurrent attacks of exertion-induced hemiplegic migraine. Since the hemiparetic attacks were exertion induced, they were initially ascribed to recurrent transient ischemic attacks. However, the clinical picture, normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), lack of response to treatment with antiplatelets and anticoagulants, and successful treatment with verapamil suggested that the hemiparesis was not due to ischemia, but was indeed a migraine aura. We suggest that exertion induced the aura of hemiparesis by lowering the threshold for the development of cortical spreading depression. Even though our patient had no family history of hemiplegic migraine, a mutation in an ion channel gene (eg, the CACNA1A gene on chromosome 19) might account for his episodic attacks. CONCLUSION: Migraine aura should be included in the differential diagnosis of exertion-induced focal neurologic deficit. 相似文献
5.
Sandrine Bourgeois Richard Harvey Professor Elias Fattal 《American Journal of Drug Delivery》2005,3(3):171-204
Most therapeutic peptides and proteins are administered via the parenteral route, which presents numerous drawbacks and limitations. To overcome these drawbacks, alternative administration routes, such as oral or mucosal routes, have been investigated. The oral route presents a series of attractive advantages for the administration of therapeutic compounds, such as the avoidance of the pain and discomfort associated with injections, good patient compliance, and being less expensive to produce. However, oral administration of peptides, proteins, or nucleic acids also presents several difficulties because of their instability in the upper gastrointestinal (GI) tract and their poor transport across biologic membranes. Among the various approaches developed to improve the oral delivery of peptides, proteins, or nucleic acids, specific delivery to the colon has attracted a lot of interest because of its potential for the local treatment of colonic diseases, systemic delivery of poorly absorbed drugs, and vaccine delivery. Numerous pharmaceutical approaches described in this review have been exploited for the development of colon-targeted drug delivery systems using various concepts, such as pH-dependent, time-dependent, pressure-controlled, or bacterially triggered delivery systems. The action of the pH-dependent delivery systems is based on pH differences between the stomach and the ileum. Time-dependent delivery systems are based on the transit time of pharmaceutical dosage forms in the GI tract, drug release being delayed until they reach the colon. A combination of pH- and time-dependent delivery systems has also been described to avoid the drawbacks of both strategies. The pressure-controlled delivery concept exploits the physiologic luminal pressure of the colon as the driving force for site-specific delivery of drugs. Finally, bacterially triggered delivery systems exploit the enormous diversity of enzymatic activity associated with the colonic microflora. Bacterially triggered delivery systems are generally composed of polymers, which are specifically degraded by colonic enzymes of microbial origin. These polymers have been used to form prodrugs with the drug moiety, as coating materials for the drug core, or as embedding media to entrap the drug into matrix or hydrogel systems. Each of these concepts has advantages and limitations. They present varied colonic specificity and, among them, bacterially triggered delivery systems in particular show the greatest potential for colonic delivery of peptides, proteins, and nucleic acids. 相似文献
6.
7.
Ittai Fattal Noam Shental Yair Molad Armando Gabrielli Elisheva Pokroy‐Shapira Shirly Oren Avi Livneh Pnina Langevitz Rachel Pauzner Ofer Sarig Uzi Gafter Eytan Domany Irun R. Cohen 《Immunology》2014,141(2):276-285
Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities – anti‐dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two‐thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two‐thirds of SLE patients reacted to a large spectrum of self‐molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein–Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease. 相似文献
8.
Maria Papaiordanidou PhD Mitsuhiro Hayashibe PhD Alain Varray PhD Charles Fattal MD PhD David Guiraud PhD 《Muscle & nerve》2014,50(4):556-563
Introduction: The purpose of this study was to propose a method that allows extraction of the current muscle state under electrically induced fatigue. Methods: The triceps surae muscle of 5 subjects paralyzed by spinal cord injury was fatigued by intermittent electrical stimulation (5 × 5 trains at 30 Hz ). Classical fatigue indices representing muscle contractile properties [peak twitch (Pt) and half‐relaxation time (HRT)] were assessed before and after each 5‐train series and were used to identify 2 relevant parameters (Fm, Ur) of a previously developed mathematical model using the Sigma‐Point Kalman Filter. Results: Pt declined significantly during the protocol, whereas HRT remained unchanged. Identification of the model parameters with experimental data yielded a model‐based fatigue assessment that gave a more stable evaluation of fatigue than classical parameters. Conclusions: This work reinforces clinical research by providing a tool that clinicians can use to monitor fatigue development during stimulation. Muscle Nerve 50: 556–563, 2014 相似文献
9.
Ludivine Bol Jean-Christophe Galas Hervé Hillaireau Isabelle Le Potier Valérie Nicolas Anne-Marie Haghiri-Gosnet Elias Fattal Myriam Taverna 《Biomedical microdevices》2014,16(2):277-285
We describe a compartmentalized microdevice specifically designed to perform permeability studies across a model of lung barrier. Epithelial cell barriers were reproduced by culturing Calu-3 cells at the air-liquid interface (AIC) in 1 mm2 microwells made from a perforated glass slide with an embedded porous membrane. We created a single basolateral reservoir for all microwells which eliminated the need to renew the growth medium during the culture growth phase. To perform drug permeability studies on confluent cell layers, the cell culture slide was aligned and joined to a collection platform consisting in 35 μL collection reservoirs connected at the top and bottom with microchannels. The integrity and functionality of the cell barriers were demonstrated by measurement of trans-epithelial electrical resistance (TEER), confocal imaging and permeability assays of 14C-sucrose. Micro-cell barriers were able to form confluent layers in 1 week, demonstrating a similar bioelectrical evolution as the Transwell systems used as controls. Tight junctions were observed throughout the cell-cell interfaces, and the low permeability coefficients of 14C-sucrose confirmed their functional presence, creating a primary barrier to the diffusion of solutes. This microdevice could facilitate the monitoring of biomolecule transport and the screening of formulations promoting their passage across the pulmonary barrier, in order to select candidates for pulmonary administration to patients. 相似文献
10.
Aurélie Spagnul Céline Bouvier-Capely Guillaume Phan Géraldine Landon Christine Tessier David Suhard François Rebière Michelle Agarande Elias Fattal 《European journal of pharmaceutics and biopharmaceutics》2011,79(2):258-267
Cutaneous contamination by radionuclides is a major concern in the nuclear industry. In case of skin exposure to uranium, no efficient emergency treatment is available to remove the actinide from the skin. For this purpose, we developed a nanoemulsion containing calixarene molecules displaying good chelating properties towards uranium. In this paper, we describe the ability of this formulation to trap uranium and limit its transfer from the cutaneous contaminated site into the blood. Uranium percutaneous diffusion kinetics was assessed with Franz cells over 24 h through intact and excoriated pig ear skin biopsies, after or without application of the nanoemulsion. Uranium distribution in the skin layers was analysed by SIMS microscopy. The results showed that prompt application of the calixarene nanoemulsion allows a 94% and 98% reduction of the amount of uranium diffused respectively through intact and excoriated skin. The formulation is still efficient in case of delayed application up to 30 minutes since the 24 h-uranium transfer through excoriated skin is reduced by 71%. Besides, no accumulation of uranium or uranium-calixarene chelate was observed in the different skin layers. In conclusion, this study demonstrated the efficiency of the calixarene nanoemulsion, which can be regarded as a promising treatment for uranium cutaneous contamination. 相似文献