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  • European Journal of Pharmaceutics and Biopharmaceutics
  • 1
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, 2005, Vol.59(1), pp.242-242
    Keywords: Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
    Source: ScienceDirect Journals (Elsevier)
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  • 2
    Language: English
    In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, January 1998, Vol.45(1), pp.23-9
    Description: Collagen microparticles were evaluated as a carrier system for glucocorticoids, and their physicochemical characteristics were determined. The particles were prepared by emulsifying and cross-linking native collagen. Particles in a size range of about 10 microns were obtained. The particle charge was dependent on the pH. A positive charge resulted when the surrounding medium had a pH below 4.5 and a negative charge with a pH above 4.5. This charge determined the magnitude of the interaction with dissolved charged drugs. The positively charged drug, prednylidene diethylaminoacetate, bound significantly to the particles above pH 4.5, whereas the negatively charged prednisolone sodium phosphate was bound below this pH. Adsorption of uncharged lipophilic drugs such as hydrocortisone was largely independent of the pH. The adsorption isotherm for this drug was determined and found to follow a Langmuir adsorption isotherm. The release and stability of the microparticle system was tested with hydrocortisone only, because of its pH-independent binding properties to the particles. The liberation of this drug was not influenced by the pH of the release medium. Binding to the particles did not effect the stability of hydrocortisone. The results of this study demonstrate that collagen microparticles can be successfully used as a carrier system for lipophilic steroids.
    Keywords: Drug Compounding ; Anti-Inflammatory Agents -- Administration & Dosage ; Collagen -- Chemistry ; Glucocorticoids -- Administration & Dosage
    ISSN: 0939-6411
    E-ISSN: 18733441
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  • 3
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, 08/2005, Vol.60(3), pp.391-399
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejpb.2005.02.009 Byline: Alexander Bootz (a), Thomas Russ (b), Friedhelm Gores (c), Michael Karas (b), Jorg Kreuter (a) Abstract: Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and size exclusion chromatography (SEC) were employed to elucidate the chemical composition, mean number average molecular weight (M.sub.n), mean weight average molecular weight (M.sub.w), and polydispersity (PD) of poly(butyl cyanoacrylate) (PBCA) manufactured by emulsion polymerisation. Both methods gave similar results for M.sub.n, but substantial differences were observed for M.sub.w and PD, with MALDI producing consistently lower values which could not be improved by off-line coupling of SEC and MALDI. MALDI gave a more detailed view on the chemical composition of the cyanoacrylate and revealed the presence of two additional polymer series with different end groups besides the expected PBCA series, which showed different retention in SEC. Their formation is explained by the secession/addition of formaldehyde from/to the regular polymer via (reverse) Knoevenagel reaction. In additional experiments, the influence of different pH on PBCA-NP during polymerisation was examined by comparison of polymerisation yield and particle diameter to their chemical composition as revealed by the MALDI spectra. The most uniform nanoparticles, with the highest polymerisation yield, narrowest particle size, and mass distribution were produced at pH 1. Author Affiliation: (a) Institut fur Pharmazeutische Technologie, Johann Wolfgang Goethe-Universitat, Frankfurt am Main, Germany (b) Institut fur Pharmazeutische Chemie, Johann Wolfgang Goethe-Universitat, Frankfurt am Main, Germany (c) Polymer Standards Service GmbH, Mainz, Germany Article History: Received 20 October 2004; Accepted 18 February 2005
    Keywords: Formaldehyde -- Analysis ; Nitriles -- Analysis ; Mass Spectrometry -- Analysis ; Polymers -- Analysis ; Chromatography -- Analysis ; Nanoparticles -- Analysis;
    ISSN: 09396411
    E-ISSN: 18733441
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  • 4
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, 1997, Vol.44(2), pp.127-132
    Description: Reticuloendothelial cells play an important role in the immunopathogenesis of AIDS. For this reason, a targeted delivery of antiviral drugs to these cells should significantly improve therapy of AIDS. The objective of the present study was to investigate the possibility of specific drug targeting of antiviral drugs to the reticuloendothelial cells by the oral route. Hexylcyanoacrylate nanoparticles were used as colloidal drug carriers for azidothymidine (AZT). 14 C-labelled AZT was bound to nanoparticles using bis(2-ethylhexyl) sulfosuccinate sodium as surfactant. The radioactivity in several organs including those containing large numbers of macrophages was measured after peroral administration of the nanoparticle preparation and compared to a [ 14 C]AZT control solution containing the same components without the nanoparticles. In the liver the area under the curve (AUC) of [ 14 C]AZT was 30% higher when the drug was bound to nanoparticles than after administration of the solution. In addition, higher [ 14 C]AZT concentrations were observed after 1 hour and at later time points in blood and brain when nanoparticles were used compared to the control solution. These results indicate that nanoparticles are a promising drug targeting system for nucleoside analogues. Furthermore, the increase in drug availability at sites containing abundant macrophages, e.g. in the blood and in the brain, may allow a reduction in dosage and a decrease in systemic toxicity.
    Keywords: AZT ; Body Distribution ; Drug Targeting ; Nanoparticles ; Macrophages ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
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  • 5
    Language: English
    In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, May 2000, Vol.49(3), pp.303-7
    Description: The possibility of preparing protein nanoparticles followed by covalent linkage of avidin was investigated. Free sulfhydryl groups were introduced onto the surface of protein nanoparticles either by aldehyde quenching with cysteine or reaction of free amino groups with 2-iminothiolane. The number of...
    Keywords: Avidin -- Chemistry ; Biotin -- Administration & Dosage ; Peptide Nucleic Acids -- Administration & Dosage
    ISSN: 0939-6411
    E-ISSN: 18733441
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  • 6
    Language: English
    In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, March 2000, Vol.49(2), pp.103-9
    Description: A novel non-competitive NMDA receptor antagonist MRZ 2/576 is a potent but rather short-acting (5-15 min) anticonvulsant following intravenous administration to mice as estimated by the prevention of maximal electroshock induced convulsions. This is most probably due to a rapid elimination of the drug...
    Keywords: Drug Delivery Systems ; Anticonvulsants -- Administration & Dosage ; Enbucrilate -- Administration & Dosage ; Excitatory Amino Acid Antagonists -- Administration & Dosage ; Phthalazines -- Administration & Dosage ; Receptors, N-Methyl-D-Aspartate -- Antagonists & Inhibitors
    ISSN: 0939-6411
    E-ISSN: 18733441
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  • 7
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, 1999, Vol.47(3), pp.203-213
    Description: Conventional nanoparticles based on acrylic compounds are lipophilic and possess a negative surface charge. This is due to their manufacturing process and to the chemical structure of the polymer. Hence, these particles are not suitable for the adsorption of hydrophilic anionic drugs. In the present investigation, positively charged copolymer nanoparticles prepared from aminoalkyl- and methylmethacrylates were evaluated, with regard to their physical properties. This report provides a detailed description of the synthesis of the non-commercially available monomers and their polymerization procedure. Various parameters were investigated, such as comonomer content, total amount of monomer, concentration of the radical initiator, and the composition of the polymerization medium. The resulting particle diameter and the surface charge were found to be strongly dependent on the polymerization conditions and on the pH. Optimization of the polymerization procedure yielded nanoparticles of about 200 nm exhibiting a positive surface charge. The charges of the different copolymer particles were then compared at different pH values. N-trimethylaminoethylmethacrylate (TMAEMC) nanoparticles with quaternary ammonium groups located at their surfaces, possessed a nearly constant positive zeta potential at various pH values and, consequently, pH-independent particle diameters. The physical characteristics of the other aminoalkyl copolymers correlated with the basicity of the monomers employed and were found to be strongly dependent on the pH of the dispersion medium. Aminoethylmethacrylate (AEMC), methylaminoethylmethacrylate (MMAEMC), and aminohexylmethacrylate (AHMC) as well as aminoethylmethacrylamide (AHMAC) copolymer nanoparticles exhibited a strong positively charged surface even at physiological pH and, therefore, are useful candidates for the adsorption of anionic drugs.
    Keywords: Nanoparticles ; Copolymer ; Aminoalkylmethacrylate ; Methylmethacrylate ; Surface Charge ; Physicochemical Characterization ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
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  • 8
    Language: English
    In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, May 2000, Vol.49(3), pp.203-10
    Description: The purpose of this study was the investigation of cationic nanoparticles as drug delivery systems for antisense oligonucleotides. Cationic monomethylaminoethylmethacrylate (MMAEMA) copolymer nanoparticles were prepared from N-monomethylaminoethylmethacrylate hydrochloride and methylmethacrylate. Oligonucleotides...
    Keywords: Oligonucleotides, Antisense -- Administration & Dosage
    ISSN: 0939-6411
    E-ISSN: 18733441
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  • 9
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, 1999, Vol.48(1), pp.1-12
    Description: Aminoalkylmethacrylate methylmethacrylate copolymer nanoparticles were evaluated for their use as potential drug carrier systems. Their cytotoxicity, as well as the loading of antisense oligonucleotides that were employed as anionic model drugs depended on the substitution of the basic aminoalkyl copolymer. Toxic influences on the integrity of cell membranes depended on aminoalkyl groups located on the particle surfaces. Toxicity was observed either by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays using African green monkey kidney (AGMK) cells or by a hemolysis test, where the efflux of haemoglobin from disrupted erythrocytes was measured. The cytotoxic effects were increased by the elongation of the N -alkyl chain by four additional methylene groups. Lipophilic polymethylmethacrylate (PMMA) homopolymer nanoparticles showed a negative surface charge and, therefore, were not suitable for the adsorption of anionic drugs. The surface charge was changed to positive values by the incorporation of basic monomers. Consequently, the loading efficacy was increased by raising the basic copolymer portion. Additionally, a pH-dependent loading behaviour of oligonucleotides was observed. Substitution of the amino nitrogen protons by methyl groups led to a decreased oligonucleotide loading and to a reduced cytotoxicity. Nanoparticles with permanent positively charged quarternary ammonium groups showed a high pH-independent loading efficacy, but also possessed a high cytotoxic potential. In this study, cationic copolymer nanoparticles containing 30% (w/w) methylaminoethyl-methacrylate (MMAEMC) were found to be optimal with regard to biocompatibility and carrier properties for hydrophilic anionic antisense oligonucleotides. A significant portion of adsorbed oligonucleotides were protected from enzymatic degradation. The cellular uptake of oligonucleotides into Vero cells was significantly enhanced by this methylaminoethyl-methacrylate derivative.
    Keywords: Nanoparticles ; Aminoalkylmethacrylate ; Methylmethacrylate ; Surface Charge ; Antisense Oligonucleotides ; Loading Efficacy ; 3-[4,5-Dimethylthiazol-2-Yl]-2,5-Diphenyltetrazolium Bromide ; Hemolysis ; Cell-Uptake ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
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  • 10
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, May 2014, Vol.87(1), pp.132-141
    Description: Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235 ± 19 nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24 h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma.
    Keywords: Human Serum Albumin ; Nanoparticles ; Human Hepatocellular Carcinoma (Hcc) ; Magnetic Resonance Imaging (Mri) ; Gd-Dtpa ; Rhodamine 123 ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
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