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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and Pharmacodynamic Aspects of an Ophthalmic Pilocarpine Nanoparticle-Delivery-System (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1435-1442 
    Details
    ISSN: 1573-904X
    Keywords: pilocarpine ; glaucoma ; nanoparticles ; betamethasone ; miosis ; intraocular pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The regional pharmacokinetics as well as the pharmacodynamics of pilocarpine-loaded nanoparticles for the treatment of glaucoma were investigated and compared to a solution of this drug. Poiybutylcy-anoacrylate nanoparticles were prepared by an emulsion polymerization process. Formulations with different drug concentrations (2–6%) as well as different particle concentrations were investigated and analyzed for size and drug loading. Drug binding to the particles was achieved at a level of 10–18% of the total drug content. The colloidal nanoparticles were sufficiently small (diameter: 100–300 nm) for a non-irritating application to the eye. All preparations were applied to the eyes of New Zealand white rabbits which were treated with betamethasone before to create an elevated intraocular pressure (IOP). Pilocarpine concentrations, assayed from aqueous humor using gaschromatography, increased by 23% (AUC) for nanoparticle suspensions compared to aqueous reference solutions. Additionally, t1/2 was prolonged and the elimination coefficient was significantly decreased. Pharmacodynamic effects such as miosis and IOP reduction were investigated. tmax values of aqueous humor concentration were observed to be in a similar time range as miosis tmax readings. It was found that at lower drug contents a more pronounced prolongation of miosis was achieved with nanoparticles versus a standard solution. The lOP-reduction was significantly prolonged with nanoparticles preparations; whereas maximum reduction was obtained with a reference solution after 1–2 hours, it was reached with nanoparticles at about 2–3 hours. Differences between nanoparticles and aqueous solutions were most pronounced at lower drug concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018995923348
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  • 2
    Electronic Resource
    Electronic Resource
    The Role of Serum Complement on the Organ Distribution of Intravenously Administered Poly (methyl methacrylate) Nanoparticles: Effects of Pre-Coating with Plasma and with Serum Complement (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1055-1058 
    Details
    ISSN: 1573-904X
    Keywords: nanoparticles ; body distribution ; plasma proteins ; complement ; reticulo-endothelial system ; opsonization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. 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). Methods. 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 particles's distribution was measured as described above. Results. 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. Conclusions. 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016010808522
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  • 3
    Electronic Resource
    Electronic Resource
    Significant Transport of Doxorubicin into the Brain with Polysorbate 80-Coated Nanoparticles (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1564-1569 
    Details
    ISSN: 1573-904X
    Keywords: brain tumors ; brain targeting ; doxorubicin ; nanoparticles ; polysorbate 80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i v. injection in form of 4 preparations : 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly (butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween® 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (〉6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (〈 0.1 |μg/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018983904537
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  • 4
    Electronic Resource
    Electronic Resource
    Delivery of Loperamide Across the Blood-Brain Barrier with Polysorbate 80-Coated Polybutylcyanoacrylate Nanoparticles (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 325-328 
    Details
    ISSN: 1573-904X
    Keywords: loperamide ; nanoparticles ; polysorbate 80 ; drug delivery ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. Methods. Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. Results. Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. Conclusions. Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012098005098
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  • 5
    Electronic Resource
    Electronic Resource
    Phagocytosis of Nanoparticles by Human Immunodeficiency Virus (HlV)-Infected Macrophages: A Possibility for Antiviral Drug Targeting (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 541-546 
    Details
    ISSN: 1573-904X
    Keywords: nanoparticles ; human immunodeficiency virus (HIV) ; macrophage ; drug targeting ; phagocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. The uptake of different, radioactively labeled nanoparticles (NP) made of polyalkylcyanoacrylate, polymethylmethacrylate (PMMA), and human serum albumin (HSA) by the macrophages was determined. In addition, the influence on phagocytosis of size and composition, concentration, and surface of the NP was studied. Further, macrophages of different state of activation were tested. NP made of polyhexylcyanoacrylate (PHCA) or human serum albumin with a diameter of about 200 nm were found most useful for targeting antiviral substances such as azidotymidine to macrophages. Cells infected in vitro with HIV-1D117/III, a monocytotropic HIV isolate from a perinatally infected child, possessed an even higher phago-cytotic activity than noninfected cells. Macrophages isolated from HIV-infected patients also showed good incorporation of NP. Thus, the concept of a specific targeting of antiviral substances to macrophages in HIV-infected individuals appears quite promising.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015852732512
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