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  • English  (235)
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  • 1
    Language: English
    In: Chromatographia, 2010, Vol.72(7), pp.659-664
    Description: Phospholipids are major constituents of biological membranes in plants and animals. Phospholipid-containing substances, such as lecithin, have also received increasing attention as emulsifiers in pharmaceutical drug delivery systems. The phospholipids phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, their lysophosphatidyl hydrolysis products and sphingomyelin, were quantified in lecithin and lecithin-containing drug-delivery emulsions. Lysophospholipids are constituents of lecithin, but their formation during thermal sterilization of the investigated drug delivery systems might contribute to the concentrations found in the emulsions. ; Includes references ; p. 659-664.
    Keywords: Phospholipids ; Lysophospholipids, Lecithin, Phosphatidylserine, Phosphatidylethanolamine And Phosphatidylcholine ; Electospray Mass Spectrometry ; Column Liquid Chromatography
    ISSN: 0009-5893
    E-ISSN: 16121112
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  • 2
    Language: English
    In: Pharmaceutical Research, 2015, Vol.32(12), pp.3986-3998
    Description: Byline: Susanne Beyer (1), Aline Moosmann (2), Astrid S. Kahnt (3), Thomas Ulshofer (4), Michael J. Parnham (4), Nerea Ferreiros (5), Sylvia Wagner (2), Matthias G. Wacker (1) Keywords: biorelevant release; Eudragit[R] RS 100; nanoparticles; peroral drug delivery; Ussing chamber Abstract: Purpose The contribution of permeability and drug release to drug targeting were investigated in the course of development of a nanosized formulation of the anti-inflammatory compound TMP-001, for the local treatment in the gastrointestinal tract. Methods TMP-001 was encapsulated by nanoprecipitation into Eudragit[R] RS 100. The permeability of these carriers was investigated in an Ussing chamber model and the release rate was determined under biorelevant conditions. Formulation toxicity and particle-cell-interaction were investigated by flow cytometry, fluorescence and electron microscopy. Furthermore, spray drying was performed. Results Effective internalization of Eudragit[R]-nanoparticles into cancer cells was demonstrated. A burst release of the nanoparticles implied poor interaction of TMP-001 with Eudragit[R]. A sustained release (70.5% release after 30 min compared to 98.0% for the API) was accomplished after spray drying yielded an increased particle size. Recovery rate of TMP-001 after spray drying was 94.2[+ or -]5.9%. Conclusion The release of API from polymeric nanoparticles contributes profoundly to the in vivo-performance of drug delivery devices in the gastrointestinal tract. The impact of drug-polymer interaction and particle size was analyzed. Sustained release of TMP-001 could only be achieved by increasing particle size. Therefore, biorelevant release testing has been demonstrated to be a valid tool for nanoformulation design. Author Affiliation: (1) Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany (2) Department of Bioprocess Technologies & Nanotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Stra[sz]e 48, 66386, St. Ingbert, Germany (3) Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany (4) Fraunhofer Institute of Molecular Biology and Applied Ecology, Project Group for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt (Main), Germany (5) Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany Article History: Registration Date: 15/07/2015 Received Date: 30/04/2015 Accepted Date: 15/07/2015 Online Date: 28/07/2015
    Keywords: biorelevant release ; Eudragit® RS 100 ; nanoparticles ; peroral drug delivery ; Ussing chamber
    ISSN: 0724-8741
    E-ISSN: 1573-904X
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  • 3
    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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  • 4
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  • 5
    Language: English
    In: PLoS ONE, 2012, Vol.7(3), p.e32568
    Description: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. ; In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different co-incubation experiments were performed with competing ligands of the respective receptor. ; This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.
    Keywords: Research Article ; Biology ; Materials Science ; Medicine ; Biotechnology ; Pharmacology ; Biochemistry
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: PLoS ONE, 2010, Vol.5(12), p.e14213
    Description: Due to the use of organophosphates (OP) as pesticides and the availability of OP-type nerve agents, an effective medical treatment for OP poisonings is still a challenging problem. The acute toxicity of an OP poisoning is mainly due to the inhibition of acetylcholinesterase (AChE) in the peripheral and central nervous systems (CNS). This results in an increase in the synaptic concentration of the neurotransmitter acetylcholine, overstimulation of cholinergic receptors and disorder of numerous body functions up to death. The standard treatment of OP poisoning includes a combination of a muscarinic antagonist and an AChE reactivator (oxime). However, these oximes can not cross the blood-brain barrier (BBB) sufficiently. Therefore, new strategies are needed to transport oximes over the BBB. ; In this study, we combined different oximes (obidoxime dichloride and two different HI 6 salts, HI 6 dichloride monohydrate and HI 6 dimethanesulfonate) with human serum albumin nanoparticles and could show an oxime transport over an BBB model. In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes. ; With these nanoparticles, for the first time, a tool exists that could enable a transport of oximes over the BBB. This is very important for survival after severe OP intoxication. Therefore, these nanoparticulate formulations are promising formulations for the treatment of the peripheral and the CNS after OP poisoning.
    Keywords: Research Article ; Biotechnology ; Neurological Disorders ; Pharmacology -- Drug Development
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(3), p.e92068
    Description: This study was performed to explore the feasibility of tracing nanoparticles for drug transport in the healthy rat brain with a clinical MRI scanner. Phantom studies were performed to assess the R1 ( =  1/T1) relaxivity of different magnetically labeled nanoparticle (MLNP) formulations that were based on biodegradable human serum albumin and that were labeled with magnetite of different size. In vivo MRI measurements in 26 rats were done at 3T to study the effect and dynamics of MLNP uptake in the rat brain and body. In the brain, MLNPs induced T1 changes were quantitatively assessed by T1 relaxation time mapping in vivo and compared to post-mortem results from fluorescence imaging. Following intravenous injection of MLNPs, a visible MLNP uptake was seen in the liver and spleen while no visual effect was seen in the brain. However a histogram analysis of T1 changes in the brain demonstrated global and diffuse presence of MLNPs. The magnitude of these T1 changes scaled with post-mortem fluorescence intensity. This study demonstrates the feasibility of tracking even small amounts of magnetite labeled NPs with a sensitive histogram technique in the brain of a living rodent.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    Language: English
    In: PloS one, 2018, Vol.13(9), pp.e0204318
    Description: Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin. A microneedling device was used to treat full-thickness 3D skin models. Specimens were harvested at specified time points and qRT-PCR and microarray studies were performed. Frozen sections were examined histologically. Microneedling treatment caused morphological changes in the skin model resulting in an almost complete recovery of the epidermis five days after treatment. Microarray analysis identified an upregulation of genes that are associated with tissue remodeling and wound healing (e.g. COL3A1, COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1), immune cell recruitment (CCL11), and a member of the heat shock protein family (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory cytokines (e.g. IL1α, IL1β, IL24, IL36γ, IL36RN), and antimicrobial peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR analyses. We present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. This data suggests that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as ablative laser therapies.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Engineering And Technology ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences;
    E-ISSN: 1932-6203
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  • 9
    Language: English
    In: Chromatographia, 2010, Vol.72(7), pp.659-664
    Description: Phospholipids are major constituents of biological membranes in plants and animals. Phospholipid-containing substances, such as lecithin, have also received increasing attention as emulsifiers in pharmaceutical drug delivery systems. The phospholipids phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, their lysophosphatidyl hydrolysis products and sphingomyelin, were quantified in lecithin and lecithin-containing drug-delivery emulsions. Lysophospholipids are constituents of lecithin, but their formation during thermal sterilization of the investigated drug delivery systems might contribute to the concentrations found in the emulsions.
    Keywords: Column liquid chromatography ; Electospray mass spectrometry ; Phospholipids ; Lysophospholipids, lecithin, phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine
    ISSN: 0009-5893
    E-ISSN: 1612-1112
    Source: Springer Science & Business Media B.V.
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  • 10
    Language: English
    In: Toxicology in Vitro, December 2011, Vol.25(8), pp.1557-1567
    Description: ► We compared the cytotoxicity of TP and TP-PM on Jurkat and HT29 cells. ► TP and TP-PM could induce an inhibition of cell growth and proliferation in both tumor cell lines. ► TP and TP-PM induced apoptosis and caused activation of caspase 3/7. ► TP-PM induced in tested cell lines stronger effects than TP. Triptolide (TP), a diterpenoid triepoxide purified from the Chinese herb Hook F is characterized by strong anti-tumor effects on various cancer cells. Except its anti-tumor effects, TP also shows multiple pharmacological side activities, such as anti-inflammatory, immune-suppressive and male anti-fertility. In order to reduce these side effects, especially the immuno-suppressive activity when used to cure cancer, a novel polymeric micelle system containing TP (TP-PM) was constructed. The immune-modulation effects of TP-PM have been evaluated by previous studies. In this study, we compared the cytotoxicity of TP and TP-PM on Jurkat and HT29 cells. Therefore, we determined the cell viability, membrane integrity, cell proliferation, apoptosis, and caspase 3/7 activity after exposure to TP and TP-PM. The results demonstrated that actually low concentrated TP and TP-PM could induce an inhibition of cell growth and proliferation as well as membrane damage in both tumor cell lines. TP and TP-PM induced apoptosis and caused activation of caspase 3/7 even at low concentrations. Both formulations destroyed the membrane of Jurkat cells, nevertheless, TP-PM showed stronger pernicious effects. In general, TP-PM induced in both tested cell lines stronger effects than TP. Therefore, polymeric micelles can be considered as promising carriers for TP in cancer therapy.
    Keywords: Cytotoxicity ; Triptolide ; Polymeric Micelles ; In Vitro ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry ; Public Health
    ISSN: 0887-2333
    E-ISSN: 1879-3177
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