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  • Blood-Brain Barrier
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  • 1
    Article
    Article
    Language: English
    In: International Journal of Pharmaceutics, 02/22/2007, Vol.331(1), pp.1-10
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ijpharm.2006.10.021 Byline: Jorg Kreuter Keywords: Nanoparticles; Historical development Abstract: The historical development of nanoparticles starting with Paul Ehrlich and then first attempts by Ursula Scheffel and colleagues and the extensive work by the group of Professor Peter Speiser at the ETH Zurich in the late 1960s and early 1970s are described from a personal point of view. Special attention is given to the years between 1970 and the early 1980s. Further developments resulting from this work are also followed, and focus is placed on especially interesting improvements such as nanoparticles for the delivery of drugs across the blood-brain barrier (BBB) and PEGylated nanoparticles with a prolonged blood circulation time. Author Affiliation: Institut fur Pharmazeutische Technologie, Biozentrum, J.W. Goethe-Universitat, D-60439 Frankfurt, Germany Article History: Received 4 October 2006; Accepted 10 October 2006
    Keywords: Nanotechnology ; Nanoparticles;
    ISSN: 03785173
    E-ISSN: 18733476
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  • 2
    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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  • 3
    Language: English
    In: Journal of Nanoneuroscience, December 2009, Vol.1(2), pp.144-151
    Description: Previous investigations have shown that doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (Tween® 80) is able to cross the blood-brain barrier upon intravenous administration and is effective against intracranially implanted 101/8 glioblastoma multiforme in rats at the treatment regimen of 3 × 1.5 mg/kg (as doxorubicin) on days 2, 5, 8 post tumour implantation. The objective of the present study was to investigate the possibility to further prolong the survival of rats with 101/8 glioblastoma by extending the treatment regimen. Doxorubicin-loaded poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 were injected using two different therapeutic regimens. Two groups received four injections at the dose of 1.5 mg/kg (as doxorubicin) on days 2, 5, 8, and 16 post tumour implantation and two other groups received an additional injection on day 20 (5 × 1.5 mg/kg). Histological and immunohistochemical analyses were carried out 24 and 30 days after tumour inoculation to assess the effect of the different therapy regimens in comparison to an untreated control group. The results demonstrate that the extended chemotherapy provided an enhanced survival. Comparison of the treatment outcomes revealed that the five-injection regimen produced a more distinctive antitumor effect manifested as a decreased tumour area and proliferation index as well as a decreased necrotic area and a smaller vascular network. Tumour regression was achieved in approximately 40% of the treated animals. These results demonstrate the promising therapeutic potential of doxorubicin-loaded nanoparticles for systemic chemotherapy of human glioblastoma multiforme.
    Keywords: Doxorubicin ; Poly(Butyl Cyanoacrylate) Nanoparticles ; Drug Delivery ; Cancer Chemotherapy ; Glioblastoma ; Histology ; Histology
    ISSN: 1939-0637
    E-ISSN: 19390653
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  • 4
    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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  • 5
    Language: English
    In: Advanced drug delivery reviews, 23 March 2001, Vol.47(1), pp.65-81
    Description: The blood--brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides. One of the possibilities to overcome this barrier is a drug delivery to...
    Keywords: Blood-Brain Barrier -- Physiology ; Brain -- Metabolism ; Drug Carriers -- Pharmacokinetics ; Endothelium, Vascular -- Metabolism ; Polysorbates -- Pharmacokinetics ; Surface-Active Agents -- Pharmacokinetics
    ISSN: 0169-409X
    E-ISSN: 18728294
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  • 6
    Language: English
    In: Journal of Controlled Release, 1997, Vol.49(1), pp.81-87
    Description: The ability of 12 different surfactants, coated onto the surface of nanoparticles, to facilitate the delivery of a nanoparticle-bound model drug, dalargin, was investigated. The leu-enkephalin analogue hexapeptide dalargin was bound to polybutylcyanoacrylate nanoparticles by sorption for 3 h. Different surfactants were then coated over these nanoparticles and were injected intravenously into mice. Nociceptive analgesia was then measured by the tail-flick text 15, 30, 45 and 90 min after injection. Only nanoparticles that had been coated with polysorbate 20, 40, 60 and 80 yielded a significant effect. The highest effect was observed with polysorbate 80. Maximum effects were found after 15 min, at a dalargin dosage of 10 mg/kg, and after 45 min, with 7.5 mg/kg.
    Keywords: Nanoparticles ; Surfactants ; Polysorbate ; Brain Delivery ; Blood–Brain Barrier ; Enkephalin ; Dalargin ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0168-3659
    E-ISSN: 1873-4995
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  • 7
    Language: English
    In: Pharmaceutical research, November 2001, Vol.18(11), pp.1613-9
    Description: The aim of this study was to investigate the different pharmacokinetic behavior of surface-modified poly(methylmethacrylate) (PMMA) nanoparticles. The particles were 14C-labeled and coated with polysorbate 80, poloxamer 407, and poloxamine 908. Plain particles served as control particles. In vivo studies were performed in three tumor models differing in growth, localization, and origin. Particle suspensions were administered via the tail vein, and at given time animals were killed and organs were dissected for determination of PMMA concentration. For the PMMA nanoparticles coated with poloxamer 407 or poloxamine 908, high and long-lasting concentrations were observed in the melanoma and at a lower level in the breast cancer model. In an intracerebrally growing glioma xenograft, the lowest concentrations that did not differ between the tumor-loaded and tumor-free hemispheres were measured. Organ distribution of the four investigated batches differed significantly. For instance, poloxamer 407- and poloxamine 908-coated particles circulated over a longer period of time in the blood, leading additionally to a higher tumor accumulation. In contrast, plain and polysorbate 80-coated particles accumulated mainly in the liver. The strong expression of vascular endothelial growth factor and Flk-1 in the melanoma correlated with high concentrations of PMMA in this tumor. The degree of accumulation of PMMA nanoparticles in tumors depended on the particle surface properties and the specific growth differences of tumors.
    Keywords: Breast Neoplasms -- Drug Therapy ; Glioblastoma -- Drug Therapy ; Melanoma, Experimental -- Drug Therapy ; Polymethyl Methacrylate -- Chemistry ; Surface-Active Agents -- Chemistry
    ISSN: 0724-8741
    E-ISSN: 1573904X
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  • 8
    Article
    Article
    Language: English
    In: European journal of drug metabolism and pharmacokinetics, 1994, Vol.19(3), pp.253-6
    Description: Nanoparticles are colloidal polymeric particles (size 〈 1000 nm) to which drugs are bound by sorption, incorporation, or chemical binding. After intravenous injection they normally distribute into the organs of the reticuloendothelial system (liver, spleen, lungs, bone marrow). However, their body distribution can be altered by coating with surfactants or with physiological components such as serum complement factors. The influence of these coatings on the body distribution and possible mechanisms for the alteration of this distribution are discussed. Differently coated nanoparticles can be used for the targeting of bound drugs to tumors, to the brain, and to inflamed areas in the body.
    Keywords: Drug Carriers ; Polymers -- Administration & Dosage
    ISSN: 0378-7966
    E-ISSN: 21070180
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  • 9
    Language: English
    In: Brain research, 13 March 1995, Vol.674(1), pp.171-4
    Description: Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an analgesic effect. All controls, including a simple mixture of the three components (drugs, nanoparticles, and surfactant) mixed directly before i.v. injection, exhibited no effect. Analgesia was also prevented by pretreatment with naloxone. Fluorescent and electron microscopic studies indicated that the passage of the particle-bound drug occurred by phagocytic uptake of the polysorbate 80-coated nanoparticles by the brain blood vessel endothelial cells.
    Keywords: Blood-Brain Barrier ; Colloids -- Pharmacokinetics ; Peptides -- Pharmacokinetics ; Polymers -- Pharmacokinetics
    ISSN: 0006-8993
    E-ISSN: 18726240
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  • 10
    Language: English
    In: The Journal of pharmacology and experimental therapeutics, June 2006, Vol.317(3), pp.1246-53
    Description: Drug delivery to the brain is becoming more and more important but is severely restricted by the blood-brain barrier. Nanoparticles coated with polysorbates have previously been shown to enable the transport of several drugs across the blood-brain barrier, which under normal circumstances is impermeable to these compounds. Apolipoprotein E was suggested to mediate this drug transport across the blood-brain barrier. In the present study, apolipoprotein E was coupled by chemical methods to nanoparticles made of human serum albumin (HSA-NP). Loperamide, which does not cross the blood-brain barrier but exerts antinociceptive effects after direct injection into the brain, was used as model drug. Apolipoprotein E was chemically bound via linkers to loperamide-loaded HSA-NP. This preparation induced antinociceptive effects in the tail-flick test in ICR mice after i.v. injection. In contrast, nanoparticles linked to apolipoprotein E variants that do not recognize lipoprotein receptors failed to induce these effects. These results indicate that apolipoprotein E attached to the surface of nanoparticles facilitates transport of drugs across the blood-brain barrier, probably after interaction with lipoprotein receptors on the brain capillary endothelial cell membranes.
    Keywords: Apolipoproteins E -- Pharmacokinetics ; Blood-Brain Barrier -- Metabolism ; Drug Carriers -- Pharmacokinetics ; Loperamide -- Pharmacokinetics ; Nanostructures -- Chemistry ; Serum Albumin -- Pharmacokinetics
    ISSN: 0022-3565
    E-ISSN: 15210103
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