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  • 11
    Language: English
    In: Current Medicinal Chemistry - Central Nervous System Agents, September 2002, Vol.2(3), pp.241-249
    Description: Poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (Tween 80) enable the transport of a number of drugs across the blood-brain barrier (BBB) into the brain following intravenous injection. These drugs include the hexapeptide endorphin dalargin, the dipeptide kytorphin, loperamide, tubocurarine, doxorubicin, and the NMDAreceptor antagonists MRZ 2 / 576 and MRZ 2 / 596.After binding to the polysorbate-coated particles, dalargin as well as loperamide exhibited a dose-dependent antinociceptive effect after i.v. injection as determined by the tail-flick as well as by the hot plate test. This effect was accompanied by a Straub reaction and was totally inhibited by pretreatment with naloxone, indicating that it is a central effect and not peripheral analgesia. After brain perfusion of rats with tubocurarine bound to the polysorbate-coated nanoparticles epileptic spikes were observable in the EEC of the rats but not with the controls. Other very interesting results were obtained with the NMDA-receptor antagonists MRZ 2 / 576 and MRZ 2 / 596. The very short anticonvulsive response of MRZ 2 / 576 was increased from below 30 to 300 min, and the transport across the BBB of the non-penetrating MRZ 2 / 596 was enabled after i.v. injection. Intravenous injection of polysorbate 80-coated nanoparticles loaded with doxorubicin (5 mg / kg) achieved very high brain levels of 6 g / g brain tissue while all the controls, including uncoated nanoparticles and doxorubicin solutions mixed with polysorbate, did not reach the analytical detection limit of 0.1 g / g. Moreover, experiments with the extremely aggressive glioblastoma 101 / 8 transplanted intracranially showed a long term survival for 6 months of 40 % of the rats after intravenous injection of the polysorbate 80-coated nanoparticle preparation (3 x 1.5 mg / kg). The surviving animals were sacrificed after this time and showed total remission by histological investigation. Untreated controls died within 10 - 20 days, the animals in the six other control groups between 10 - 50 days.The mechanism of the drug transport across the blood-brain barrier with the nanoparticles requires further elucidation. The most likely mechanism at present appears to be endocytotic uptake by the brain capillary endothelial cells followed either by release of the drugs in these cells and diffusion into the brain or by transcytosis. Endocytotic uptake of the polysorbate-coated nanoparticles but not of uncoated particles has been shown with bovine, murine, rat, and human brain capillary endothelial cells. After injection of the nanoparticles, apolipoprotein E (apo E) or apo B adsorption of the particles seems to occur as already shown in vitro, followed by interaction with the LDL receptor and endocytotic uptake. This scenario is rather likely since both apolipoproteins can interact with the LDL-receptor. They may then be taken up like the naturally occurring lipoprotein particles.
    Keywords: Blood - Brain Barrier ; Nanoparticles Language: English ; Nanoparticles
    ISSN: 1568-0150
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  • 12
    Language: English
    In: Biochimica et biophysica acta, 12 January 2001, Vol.1544(1-2), pp.177-88
    Description: Protamine is a cationic peptide with a molecular mass of approx. 4000 Da that is able to condense DNA. In the present study it was used to complex antisense oligonucleotides (ODNs) and to form solid particles with initial diameters of 90-150 nm. The reaction was very rapid and occurred by simple mixing of diluted solutions of the polycation with the oligonucleotide. The aggregation was dependent on the oligonucleotide chain length and the protamine/ODN mass ratio. Particle formation required a minimal chain length of nine nucleotides and a mass ratio of 0.5:1. The particle surface charge and the number of particles depended on the mass ratio. With increasing amounts of the peptide, the number of particles and the zeta potential increased. Both negatively and positively charged particles improved the stability of oligonucleotides against DNase I digestion. Above a mass ratio of 2.5:1 no degradation was found. The uptake of unbound rhodamine-labelled ODNs and its complexes with protamine was determined with Vero cells under in vitro cell culture conditions at 37 degrees C and 4 degrees C. At 37 degrees C the cellular uptake increased with increasing mass ratio. The internalized oligonucleotides were localized in the cytoplasm and in the nucleus of the cells. When Vero cells were treated with these samples at 4 degrees C for 4 h, no fluorescence could be detected inside the cells. Therefore, our data indicate an energy dependent endocytotic uptake mechanism. In contrast, spermine and spermidine, which are also known condensation agents, did not aggregate with oligonucleotides into nanoparticles under the same conditions.
    Keywords: Oligonucleotides, Antisense -- Chemical Synthesis ; Organophosphorus Compounds -- Chemical Synthesis ; Thionucleotides -- Chemical Synthesis
    ISSN: 0006-3002
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 13
    Language: English
    In: Pharmaceutical research, July 1996, Vol.13(7), pp.1055-8
    Description: The organ distribution of radiolabeled poly (methyl methacrylate) (PMMA) nanoparticles coated with plasma proteins and serum complement in rats was studied in order to determine the effect of serum complement on the particle phagocytosis by the organs of the reticulo-endothelial system (RES). PMMA-nanoparticles were coated overnight with plasma proteins or serum complement, and injected into Wistar rats. The body distribution of nanoparticles was measured by means of scintillation counting of organ samples. In addition, proteins adsorbed to the particle surface were inactivated by heat treatment prior to injection, and the particle's distribution was measured as described above. Whereas uncoated nanoparticles (control group) were mainly taken up by the Kupffer cells in the liver, incubation of the particles in plasma for 12 h followed by heat inactivation reduced the particle concentrations in the liver to merely 22% after 30 min. After 120 min, liver concentrations were still lower than the control group, and almost 30% of the administered dose of the heat-inactivated particle group was present in non-RES organs and tissues. Particles with non-inactivated complement were accumulated in the lung at concentrations of 29% after 30 min, which increased to 71% after 120 min, whereas those coated with inactivated complement reached lung concentrations above 70% already after 30 min. Particles coated with plasma components are able to avoid uptake by the RES, especially after heat inactivation of the plasma components adsorbed. Adsorption and heat inactivation of complement proteins alone, however, does not have the same result as coating with plasma proteins followed by heat inactivation. Therefore, it is concluded that plasma components other than complement proteins take part in the process of RES activation and phagocytosis of injected nanoparticles.
    Keywords: Complement System Proteins -- Chemistry ; Mononuclear Phagocyte System -- Drug Effects ; Polymethacrylic Acids -- Pharmacology
    ISSN: 0724-8741
    E-ISSN: 1573904X
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  • 14
    In: Bone Marrow Transplantation, 2017
    Keywords: Allografts–Blood ; Bone Marrow Transplantation–Blood ; Donor Selection–Therapy ; Female–Therapy ; HLA Antigens–Therapy ; Humans–Therapy ; Isoantibodies–Therapy ; Leukemia, Myelogenous, Chronic, BCR-Abl Positive–Therapy ; Middle Aged–Therapy ; Tissue Donors–Therapy ; HLA Antigens ; Isoantibodies;
    ISSN: 0268-3369
    E-ISSN: 1476-5365
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  • 15
    In: HLA, October 2018, Vol.92(4), pp.253-254
    Description: A new allele, now named , was discovered during testing of a registry donor for possible stem cell transplantation.
    Keywords: C*02:138 ; Hla ; Ngs
    ISSN: 2059-2302
    ISSN: 00012815
    E-ISSN: 2059-2310
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  • 16
    Language: English
    In: Journal of Research Updates in Polymer Science, 2014, Vol.3(2), pp.63-85
    Description: Controlled release of drugs at the locus of the targeted disease is one of the most challenging research areas in the pharmaceutical field. Nowadays novel drug delivery systems on the basis of polymers are attracting great attention since they can improve therapeutic efficiency of potent drug prepns. decreasing the risk of side effects. By developing colloidal drug delivery systems such as liposomes¿/vesicles and polymeric nanoparticles and nanocapsules the pharmacokinetics of the drug can be changed and thus the therapeutic efficiency of the drug can be increased. Nanoparticles with their special characteristics such as small particle size, large surface area and high capacity of carrying biol. active substances offer a no. of advantages compared to other colloidal drug delivery systems. Controlled drug release systems are constructed on the basis of natural and biocompatible synthetic polymers. Among the most promising biocompatible polymers human serum albumin (HSA)¿, polyalkyl cyanoacrylates (PACA) and poly-¿D,¿L-¿lactic acid (PLA) are of great importance. Nanoparticles on their basis have been proven to be efficient in treatment of serious and long-¿termed diseases such as tumors, tuberculosis and bacterial infections. Therefore this article is aimed to give a brief review on the research works devoted to the synthesis and investigation of polymeric nanoparticles and nanocapsules based on PACA, HSA and PLA for the past three decades.
    Keywords: Drug Delivery Systems ; Nanoparticles ; Nanocapsules ; Polyalkyl Cyanoacrylates ; Human Serum Albumin ; Poly-D;L-Lactic Acid;
    ISSN: 1929-5995
    ISSN: Journal of Research Updates in Polymer Science
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  • 17
    Language: English
    In: The American Journal of Public Health, Dec, 2011, Vol.101(12), p.S188(8)
    Description: From 1999 to 2009, the Eliminating Health Disparities Pre-doctoral Fellowship Program provided specialized education and mentoring to African American graduate students in public health. Fellows received a public health degree, coursework in understanding and eliminating health disparities, experiential learning, mentored research, and professional network building with African American role models. We describe successful strategies for recruiting and training fellows and make 5 recommendations for those seeking to increase workforce diversity in public health: (1) build a community of minority students, not a string of individual recruits; (2) reward mentoring; (3) provide a diverse set of role models and mentors; (4) dedicate staffing to assure a student-centered approach; and, (5) commit to training students with varying levels of academic refinement. doi: 10.2105/AJPH.2011.300122)
    Keywords: Minority Employees -- Training ; Medical Personnel Training -- Forecasts And Trends ; Medical Personnel Training -- Management ; Public Health Administration -- Research
    ISSN: 0090-0036
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  • 18
    Language: English
    In: International Journal of Pharmaceutics, 1996, Vol.137(1), pp.67-74
    Description: Methylmethacrylate (MMA) sulfopropylmethacrylate (SPM) copolymer nanoparticles were prepared by free radical polymerization. The conditions of preparation were varied with regard to the concentration of initiator and monomer, and copolymer composition. Nanoparticles with a yield greater than 80% were produced. The particles were characterized in terms of particle size, size distribution, particle charge (zetapotential) and molecular weight. The data were compared to pure polymethylmethacrylate (PMMA) nanoparticles. The copolymer composition was shown to influence particle size and particle charge. The influence of the total monomer amount in the polymerization medium on the particle size was characteristic up to a concentration of 2% depending on the solubility of MMA in water at the temperature of reaction. An increasing amount of total monomer led to particle sizes of 60–130 nm for low monomer concentrations (0.5%), depending on the proportion of SPM (0–10%), to 120–280 nm for higher total monomer concentrations (greater than 2%). Surface charge as well as particle size were influenced mainly by the proportion of the comonomer SPM in the copolymer. The negative surface charge increased from - 52 mV for pure PMMA nanoparticles to − 80mV for the copolymer particles with an SPM content of 10%. In the same range of 0–10%), SPM of the total monomer, the particle sizes decreased from 187 to 100 run. The concentration of the initiator up to a concentration of 0.3% showed no effect on the particle size of the resulting nanoparticle suspension. Higher concentrations led to intolerably large variability in the polymerization process.
    Keywords: Nanoparticles ; Copolymer ; Methylmethacrylate (Mma) ; Sulfopropylmethacrylate (Spm) ; Physicochemical Characterization ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 19
    Language: English
    In: International Journal of Pharmaceutics, 1992, Vol.85(1), pp.7-17
    Description: The influence of various penetration enhancers including propylene glycol, oleic acid, Azone ® , isopropyl myristate, valine, and nanoparticles on the permeation coefficient for the permeation of amino acids through hairless mouse skin as well as a dialysis membrane was assessed in vitro. The two different types of membranes were employed in order to distinguish between effects due to thermodynamic parameters and those due to barrier resistance. Furthermore, the influence of these penetration enhancers on the amount of amino acids remaining within the skin was determined. Oleic acid was found to be the most efficient enhancer for amino acids (enhancement factor (EF) of 176 for histidine) followed by Azone ® (EF of 45 for phenylalanine). All other penetration enhancers failed to exert any significant effect on the skin permeation of amino acids. The fact that the enhancement effects of oleic acid and Azone ® are not reversible and that the enhancers exhibited no influence with dialysis membranes clearly indicate that both penetration enhancers induce their effects on the basis of changes in skin morphology. Choosing arginine, histidine and phenylalanine as test permeants enabled a correlation between the enhancement effects and the degree of ionization of the test permeant. Histidine is the only amino acid which is unionized at pH 7.4 due to its isoelectric point. This might be the reason why the permeation enhancement induced by valine was only detectable with histidine, and not with the other two amino acids. Neither penetration enhancer resulted in any significant effect on the amount of the amino acid accumulated in the skin.
    Keywords: Amino Acid ; Hairless Mouse Skin ; Permeability ; Penetration Enhancer ; Propylene Glycol ; Azone ® ; Oleic Acid ; Isopropyl Myristate ; Valine ; Nanoparticles ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 20
    Language: English
    In: International Journal of Pharmaceutics, 1991, Vol.72(2), pp.149-155
    Description: The permeation coefficients of protein amino acids through full-thickness hairless mouse skin were determined by means of an infinite dose technique. The permeability coefficients were found to be very low and ranged between 1 and 50 × 10 −5 (cm/h). No significant difference between ionized and unionized transdennal transport was observed. Higher permeation coefficients were clearly attributed to membrane damage caused by alkaline solutions. A significant difference between the permeation of positively and negatively charged molecules was not obvious. The permeability also did not depend on molecular weight or on the hydrophobicity of the amino acids. Hairless mouse skin did not form a reservoir for amino acids.
    Keywords: Amino Acid ; Hairless Mouse Skin ; Permeability ; Skin Reservoir ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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