Kooperativer Bibliotheksverbund

Berlin Brandenburg

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  • 1
    In: PLoS ONE, 2015, Vol.10(7)
    Description: Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.
    Keywords: Research Article
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: International Journal of Pharmaceutics, 30 January 2017, Vol.517(1-2), pp.338-347
    Description: The physico-chemical characterisation of nanoparticles is often lacking the determination of the glass transition temperature, a well-known parameter for the pure polymer carrier. In the present study the influence of water on the glass transition temperature of poly (DL-lactic-co-glycolic acid) nanoparticles was assessed. In addition, flurbiprofen and THPP as model drugs were incorporated in poly (DL-lactic-co-glycolic acid), poly (DL-lactic acid), and poly (L-lactic acid) nanoparticles. For flurbiprofen-loaded nanoparticles a decrease in the glass transition temperature was observed while THPP exerted no influence on this parameter. Based on this observation, the release behaviour of the drug-loaded nanoparticles was investigated at different temperatures. For all preparations an initial burst release was measured that could be attributed to the drug adsorbed to the large nanoparticle surface. At temperatures above the glass transition temperature an instant drug release of the nanoparticles was observed, while at lower temperatures less drug was released. It could be shown that the glass transition temperature of drug loaded nanoparticles in suspension more than the corresponding temperature of the pure polymer is the pivotal parameter when characterising a nanostructured drug delivery system.
    Keywords: Drug Delivery System ; Poly (DL-Lactic-Co-Glycolic Acid) ; Poly (Lactic Acid) ; Differential Scanning Calorimetry ; Release Profile ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 3
    Language: English
    In: International Journal of Pharmaceutics, 30 December 2015, Vol.496(2), pp.942-952
    Description: The study on cholangiocellular cell lines was conducted with THPP-loaded nanoparticles with different polymers as matrices. Nanoparticles were characterized and the effect of the carrier system was examined . Comparison of free substance, embedded substance and different materials revealed severe differences for cellular uptake and activity after activation by illumination. The photodynamic therapy with porphyrin derivatives is an established approach to targeted tumor therapy, but is still afflicted with disadvantages of the physicochemical characteristics of the photosensitizer. To overcome drug-related restrictions in photodynamic therapy, three 5,10,15,20-tetrakis( -hydroxyphenyl) porphyrin ( THPP)-loaded nanoparticulate formulations based on poly( -lactide- -glycolide) (PLGA), poly( , -lactide) (PLA), and Eudragit E were prepared in a consistent diameter range and compared with free THPP . Formulation behavior was investigated in two different cholangiocellular cell lines, EGI-1 and TFK-1. High cytotoxicity was shown for all photosensitizer loaded nanoparticle (NP) formulations and free THPP, with EC values ranging from 0.2 to 1.3 μM. PLA based NP were not as effective in all performed tests as other formulations. Nanoparticulate embedded THPP remained photodynamically active and resulted in caspase-3 activation even at low concentrations of 250 nM. PLGA based NP exhibited highest caspase-3 activation. For all formulations an effective intracellular accumulation of THPP was observed, whereby for THPP-Eudragit E-NP a 200-fold drug accumulation was shown. Polymer based nanoparticles were shown to be an effective and highly active transport vehicle for the photosensitizer THPP . Problems like low solubility of free drug can be circumvented by successful embedding into nanoparticulate carrier systems, maintaining therapeutic effects of the photosensitizer.
    Keywords: Drug Delivery System ; Photodynamic Therapy ; Cholangiocarcinoma ; Nanoparticle ; Cytotoxicity ; Polymer Influence ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 4
    Language: English
    In: Biomaterials, 2006, Vol.27(28), pp.4975-4983
    Description: Nanoparticles consisting of human serum albumin (HSA) represent a promising strategy for targeted drug delivery to tumour cells. The coupling of the antibody trastuzumab to HSA nanoparticles takes advantage of the capability of HER2-positive cells to incorporate substances binding to HER2. In our present study, we developed nanoparticles based on HSA which were covalently modified on their surface with thiolated trastuzumab. A special focus was on the optimisation of the thiolation procedure of the antibody under the aspect of an effective binding to particle surfaces. Different thiolation conditions were evaluated and the degree of antibody dimerisation was determined. We analysed the thiolated antibody by size exclusion chromatography (SEC) and identified the best thiolation procedure for the preparation of trastuzumab-conjugated nanoparticles. Over a storage period of 6 weeks the resulting particles were stable and physico-chemical properties such as size and zetapotential did not show any changes. Biological activity was confirmed under cell culture conditions: antibody-conjugated nanoparticles showed a specific targeting to HER2-overexpressing cells with cellular uptake by receptor-mediated endocytosis. These data provide the basis for the development of stable and biological active carrier systems for directed targeting of tumour cells using trastuzumab-conjugated HSA nanoparticles.
    Keywords: Albumin ; Drug Delivery ; Flow Cytometry ; Nanoparticle ; Surface Modification ; Thiol ; Medicine ; Engineering
    ISSN: 0142-9612
    E-ISSN: 1878-5905
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  • 5
    Language: English
    In: International Journal of Pharmaceutics, 14 February 2011, Vol.404(1-2), pp.308-316
    Description: The photosensitizing efficiency of human serum albumin (HSA) nanoparticles loaded with the photosensitizers meta-tetra(hydroxy-phenyl)-chlorin (mTHPC) and meta-tetra(hydroxy-phenyl)-porphyrin (mTHPP) was investigated . The endocytotic intracellular uptake, and the time dependent drug release caused by nanoparticle decomposition of the PS loaded HSA nanoparticles were studied on Jurkat cells in suspension. The photoxicity as well as the intracellular singlet oxygen ( O ) generation were investigated in dependence on the incubation time. The obtained results show that HSA nanoparticles are promising carriers for the clinical used mTHPC (Foscan). After release the ( O ) generation as well as the phototoxicity are more efficient compared with mTHPC applied without the HSA nanoparticles.
    Keywords: Pdt ; Nanocarrier ; Singlet Oxygen Generation ; Human Serum Albumin ; Phototoxicity ; Biodegradability ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 6
    Language: English
    In: Nanotechnology, 2011, Vol.22(24), p.245102 (12pp)
    Description: The second generation photosensitizer m THPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that m THPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free m THPC and m THPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost m THPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer m THPC.
    Keywords: Colonic Neoplasms -- Metabolism ; Intracellular Space -- Metabolism ; Lactic Acid -- Toxicity ; Mesoporphyrins -- Toxicity ; Nanoparticles -- Toxicity ; Polyglycolic Acid -- Toxicity;
    ISSN: 0957-4484
    E-ISSN: 1361-6528
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  • 7
    Language: English
    In: Biomacromolecules, 10 December 2018, Vol.19(12), pp.4677-4690
    Description: Aliphatic poly(carbonate)s (APCs) with rapid and controlled degradation upon specific stimulation have great advantages for a variety of biomedical and pharmaceutical applications. In the present work, we reported a new poly(trimethylene carbonate) (PTMC)-based copolymer containing multiple 4,5-dimethoxy-2-nitrobenzyl photo cleavable groups as pendent chains. The six-membered light-responsive cyclic carbonate monomer (LrM) was first prepared from 2-(hydroxymethyl)-2-methylpropane-1,3-diol and 4,5-dimethoxy-2-nitrobenzyl alcohol and then copolymerized with trimethylene carbonate (TMC) by 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) catalyzed ring-opening polymerization (ROP) to afford the light-responsive polycarbonate (LrPC). The light-triggered decomposition of LrM and LrPC was studied by NMR, UV/vis spectroscopy, and size exclusion chromatography (SEC), as well as ESI-ToF mass spectrometry. Stable monodisperse nanoparticles with hydrodynamic diameter of 100 nm could be formulated from 25% LrPC and 75% poly(lactide- co-glycolide) (PLGA) and applied for the encapsulation of temoporfin. Upon irradiation with UV light these particles displayed a significant decrease of the particle countrate and increased the release rate of temoporfin in comparison to standard PLGA nanoparticles. This work demonstrated that a combination of encapsulation of photosensitizer and light degradation using light-responsive polymers is suitable to enhance photodynamic therapy (PDT).
    Keywords: Photochemotherapy ; Drug Carriers -- Chemistry ; Nanoparticles -- Chemistry ; Polyesters -- Chemistry
    ISSN: 15257797
    E-ISSN: 1526-4602
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  • 8
    Language: English
    In: Materials Today: Proceedings, 2017, Vol.4, pp.S188-S192
    Description: In order to prepare doxorubicin-loaded nanoparticles three different preparation techniques (emulsion diffusion, solvent displacement, and double emulsion) were compared in terms of particle diameter, polydispersity, zeta potential, drug load, and drug release. The particle size and polydispersity were measured by photon correlation spectroscopy (PCS), while the amount of entrapped doxorubicin was determined by HPLC-UV. The drug release profiles were observed over 24 h at 37°C in phosphate buffered saline (PBS) containing 5% bovine serum albumin (BSA). Nanoparticles with the highest quality were obtained by using emulsion diffusion yet drug release behaviour needs to be improved.
    Keywords: Nanoparticles ; Doxorubicin ; Poly(Lactic-Co-Glycolic Acid) (Plga) ; Emulsion Diffusion ; Solvent Displacement ; Double Emulsion
    ISSN: 2214-7853
    E-ISSN: 2214-7853
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2018, Vol.13(1), p.e0189970
    Description: Symmetry is rarely found on cellular surfaces. An exception is the brush border of microvilli, which are essential for the proper function of transport epithelia. In a healthy intestine, they appear densely packed as a 2D-hexagonal lattice. For in vitro testing of intestinal transport the cell line Caco-2 has been established. As reported by electron microscopy, their microvilli arrange primarily in clusters developing secondly into a 2D-hexagonal lattice. Here, atomic force microscopy (AFM) was employed under aqueous buffer conditions on Caco-2 cells, which were cultivated on permeable filter membranes for optimum differentiation. For analysis, the exact position of each microvillus was detected by computer vision; subsequent Fourier transformation yielded the type of 2D-lattice. It was confirmed, that Caco-2 cells can build a hexagonal lattice of microvilli and form clusters. Moreover, a second type of arrangement was discovered, namely a rhombic lattice, which appeared at sub-maximal densities of microvilli with (29 ± 4) microvilli / μm2. Altogether, the findings indicate the existence of a yet undescribed pattern in cellular organization.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Sensors & Actuators: B. Chemical, 01 April 2018, Vol.258, pp.1131-1137
    Description: Immunoassays are used to detect a target analyte by using specific interaction with detection antibodies which form antigen-antibody complexes. In thermophoretic immunoassays the antigen-antibody complexes make slow thermophoresis (movement by thermal stimulation) in comparison with unbound antigens and antibodies. In this work, a sensitive thermophoretic immunoassay was demonstrated by mixing outer membrane (OM) particles of with autodisplayed Z-domains. In order to compare the influence of OM particles with autodisplayed Z-domains on the sensitivity of thermophoretic immunoassay, the conventional method only with target analyte and detection antibodies was compared with the hyper sensitive thermophoretic immunoassay by mixing OM particles with autodisplayed Z-domains, and the affinity constant was calculated. Finally, the diagnosis of inflammation by detection of a biomarker called C-reactive protein (CRP) was carried out by demonstrating the thermophoretic immunoassay for CRP based on autodisplayedZ-domains could be applied for the medical diagnosis.
    Keywords: Thermophoresis ; Autodisplay ; C-Reactive Protein ; Immunoassay ; Engineering
    ISSN: 0925-4005
    E-ISSN: 1873-3077
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