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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: 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
    Library Location Call Number Volume/Issue/Year Availability
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