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Berlin Brandenburg

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  • 1
    Language: English
    In: Journal of Controlled Release, 2011, Vol.154(1), pp.103-107
    Description: Drug delivery to the brain is restricted due to the blood–brain barrier (BBB). Previously, it has been shown that surfactant-coated doxorubicin-loaded nanoparticles were successful in overcoming the BBB and were effective in the treatment of rat brain tumours. However, drug distribution in brain tissue after crossing the BBB was never determined. To distinguish between the amounts of drug in the whole brain and the fraction of drug in the brain parenchyma after crossing the BBB a capillary depletion technique was employed. For this purpose rats were intravenously treated with a doxorubicin solution in 1% polysorbate 80, or doxorubicin-loaded poly-(n-butyl cyanoacrylate) (PBCA) nanoparticles without and with 1% polysorbate 80 coating, respectively. The dosage of doxorubicin was 5 mg per kg of rat body weight. At 30 min, 2 h, and 4 h following intravenous injection into the tail vein, the rats were sacrificed and their brains removed. Homogenates of the brains were prepared. In addition, one part of the homogenate was separated by centrifugation into a pellet (vascular elements) and supernatant (parenchyma) using a well established capillary depletion technique. The time-dependent distribution of doxorubicin in these brain fractions was studied. Clinically effective concentrations in all investigated brain fractions could only be detected in rats treated with surfactant-coated nanoparticles, indicating a significant transcytosis across the BBB. Only low concentrations were observed after 0.5 and 2 h with the uncoated nanoparticles. No uptake of doxorubicin into the brain was observable after administration of drug solution alone. These observations demonstrate the great potential of surface-coated PBCA nanoparticles for the delivery of drugs to the central nervous system. Doxorubicin concentration in different rat brain fractions 2 h after intravenous injection of 5 mg/kg doxorubicin solution, doxorubicin-loaded poly(butyl cyanoacrylate) (PBCA) nanoparticles (NP), or doxorubicin-loaded PBCA-NP coated with polysorbate 80 (PS80).
    Keywords: Nanoparticles ; Capillary Depletion ; Drug Targeting ; Blood–Brain Barrier ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0168-3659
    E-ISSN: 1873-4995
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  • 2
    Language: English
    In: PLoS ONE, 2011, Vol.6(5), p.e19121
    Description: Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB) prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods. ; The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA) or human serum albumin (PLGA/HSA) as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA) were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3×2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density. ; The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Oncology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Die Pharmazie, July 2013, Vol.68(7), pp.549-54
    Description: Lysosomal storage disorders like mucopolysaccharidosis (MPS) VI are rare diseases with a lack of well-suited treatments. Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression. Since nanoparticles (NP) have shown to be effective drug carriers, the feasibility of arylsulfatase B adsorption onto poly(butyl cyanoacrylate) (PBCA) nanoparticles was investigated in this study. In order to advance the ERT of ASB, the adsorption of the latter on the surface of PBCA NP as well as in vitro release in serum was investigated. With alteration of parameters like temperature, incubation time, pH, and enzyme amount, the adsorption process revealed to be stable with a maximum capacity of 67 microg/mg NP at a pH of 6.3. In vitro release experiments demonstrated that the adsorption is stable for at least 60 minutes in human blood serum, indicating that the ASB-loaded PBCA nanoparticles represent a promising candidate for ERT of MPS VI.
    Keywords: Enzyme Replacement Therapy ; Mucopolysaccharidosis VI -- Drug Therapy ; N-Acetylgalactosamine-4-Sulfatase -- Therapeutic Use
    ISSN: 0031-7144
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 4
    Language: English
    In: Die Pharmazie, July 2014, Vol.69(7), pp.518-24
    Description: Arylsulfatase A (ASA) deficiency is the cause of metachromatic leucodystrophy (MLD), a lysosomal storage disease associated with severe neurological disorders. Poly(butyl cyanoacrylate) (PBCA) nanoparticles overcoated with polysorbate 80 enabled the delivery of several drugs across the blood-brain barrier to the brain suggesting that these nanoparticles also may transport ASA across this barrier. The objective of this research, therefore, was to evaluate the feasibility of loading ASA onto PBCA nanoparticles. A stable ASA-loaded PBCA nanoparticle formulation was developed that could be easily freeze-dried and stored over a period of more than 8 weeks. The maximum loading capacity for this enzyme was -59 microg per 1 mg of PBCA. In the presence of 3% sucrose as a lyoprotector the activity of freeze-dried ASA was found to be 100% recoverable.
    Keywords: Cerebroside-Sulfatase -- Therapeutic Use ; Enbucrilate -- Chemistry ; Enzyme Replacement Therapy -- Methods
    ISSN: 0031-7144
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    In: Сорбционные и хроматографические процессы, 07/21/2018, Vol.18(4), pp.543-553
    ISSN: 1680-0613
    Source: CrossRef
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  • 6
    Language: English
    In: Journal of Pharmacological and Toxicological Methods, May 2017, Vol.85, pp.55-60
    Description: Capillary zone electrophoresis (CZE) was used for determination of rifabutin (RFB), an anti-tuberculosis antibiotic drug, in various pharmaceutical formulations. Apart from that, simultaneous determination of RFB and human serum albumin (HSA) was performed. Electrophoretic behaviour of RFB was examined at various pH levels. CE conditions: a quartz capillary tube (internal diameter 75 mm, effective length 50 cm, total length 60 cm), the capillary temperature was 25 °С, the voltage applied to the capillary tube was + 20 kV, the UV detection wavelength was 214 nm, hydrodynamic injection of the sample was performed at 30 mbar for 5 s, tetraborate buffer solution (0.01 М, рН 9.2). The obtained results are characterized by high efficiency (number of theoretical plates up to 260,000) and sufficient sensitivity (LOQ starting from 0.02 μg/ml for RFB). The obtained data are in good accord with both HPLC results (for RFB) and spectrophotometry (for HSA).
    Keywords: Rifabutin (Rfb) ; Human Serum Albumin (HSA) ; Capillary Electrophoresis (CE) ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 1056-8719
    E-ISSN: 1873-488X
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  • 7
    Language: English
    In: Russian Journal of Physical Chemistry A, 2015, Vol.89(5), pp.797-801
    Description: The possibility of a intermolecular complex rifabutin (RB)-2-hydroxypropyl-β-cyclodextrin (HP-β-CD) formed as a result of the interaction of the piperidine fragment of the RB molecule and the hydrophobic cavity of the HP-β-CD molecule was found. The stability constant of the intermolecular complex was determined.
    Keywords: rifabutin ; 2-hydroxypropyl-β-cyclodextrin ; complexation ; molecular modeling ; quantum-chemical calculation ; phase solubility diagram ; apparent complex stability constant
    ISSN: 0036-0244
    E-ISSN: 1531-863X
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  • 8
    Language: English
    In: International Journal of Pharmaceutics, 2007, Vol.345(1), pp.154-162
    Description: Macrophages in the lungs are the most important cell type supporting replication of in humans. The objective of this study was to investigate whether the effect of moxifloxacin against residing in macrophages could be improved by encapsulation of the drug in the biodegradable nanoparticles, which are known to accumulate in macrophages upon intravenous administration. To accomplish this, moxifloxacin was encapsulated in poly(butyl cyanoacrylate) (PBCA) nanoparticles. Encapsulated moxifloxacin accumulated in macrophages approximately three-fold times more efficiently than the free drug, and was detected in the cells for at least six times longer than free moxifloxacin at the same extracellular concentration. Inhibition of intracellular growth with encapsulated moxifloxacin was achieved at the concentration of 0.1 μg/ml, whereas the same effect with free MX required a concentration of 1 μg/ml. Nanoparticles observed within the macrophage cytoplasm were distributed throughout the cytoplasm, sometimes in the vicinity of intracellular bacteria.
    Keywords: Macrophage ; Moxifloxacin ; M. Tuberculosis ; Nanoparticles ; Poly(Butyl Cyanoacrylate) ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 9
    Language: English
    In: Journal of Controlled Release, 2007, Vol.117(1), pp.51-58
    Description: Poly(butyl cyanoacrylate) nanoparticles coated with poloxamer 188 (Pluronic® F68) and also, as shown previously, polysorbate 80 (Tween® 80) considerably enhance the anti-tumour effect of doxorubicin against an intracranial glioblastoma in rats. The investigation of plasma protein adsorption on the surface of the drug-loaded nanoparticles by two-dimensional electrophoresis (2-D PAGE) revealed that both surfactants, besides other plasma components, induced a considerable adsorption of apolipoprotein A-I (ApoA-I). It is hypothesized that delivery of doxorubicin to the brain by means of nanoparticles may be augmented by the interaction of apolipoprotein A-I that is anchored on the surface of the nanoparticles with the scavenger receptor class B type I (SR-BI) located at the blood–brain barrier. This is the first study that shows a correlation between the adsorption of apolipoprotein A-I on the nanoparticle surface and the delivery of the drug across the blood–brain barrier.
    Keywords: Apolipoprotein A-I ; Chemotherapy ; Glioblastoma ; Nanoparticles ; Poly(Butyl Cyanoacrylate) ; Poloxamer 188 ; Polysorbate 80 ; Rats ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0168-3659
    E-ISSN: 1873-4995
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  • 10
    Language: English
    In: Pharmaceutical chemistry journal, 2010, Vol.44(3), pp.151-156
    Description: The aim of the present work was to assess the influences of the parameters of the process of preparing polylactide-based nanosomal medicinal formulations of rifampicin (Rif) on nanoparticle size, the level of Rif sorption, and the kinetics of Rif release in vitro. The most effective Rif sorption in nanoparticles (up to 90%) was obtained using polylactides with additional terminal carboxyl groups. An increase in the initial Rif concentration in the organic phase from 1 to 5 mg/ml led to some decrease in the extent of sorption (from 89% to 76%) though it had no significant effect on the sizes of the resulting nanoparticles (190 - 260 nm). The rate of Rif release could be controlled by altering the composition of the polymer matrix of the nanoparticles; the presence of additional terminal carboxyl groups in polylactides gave slower antibiotic release, resulting from tighter interaction with the polymer matrix. ; Includes references ; p. 151-156.
    Keywords: Rifampicin ; Nanoparticles ; Polylactides
    ISSN: 0091-150X
    E-ISSN: 15739031
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