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G M Rodchenkov - One of the best experts on this subject based on the ideXlab platform.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration. Copyright © 2015 John Wiley & Sons, Ltd.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration.
Ekaterina Semenistaya - One of the best experts on this subject based on the ideXlab platform.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration. Copyright © 2015 John Wiley & Sons, Ltd.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration.
Paolo Giunchedi - One of the best experts on this subject based on the ideXlab platform.
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BRAIN TARGETING OF AN ANTIISCHEMIC AGENT BY Nasal Administration OF MICROPARTICLES
2015Co-Authors: Ro Dalpiaz, Luca Ferraro, Elisabetta Gavini, Paolo Giunchedi, Gaia Colombo, Fabrizio Bortolotti, Sergio Tanganelli, Angelo Scatturin, Enea Menegatti, Paolo ColomboAbstract:The adenosine derivative N6-cyclopentyladenosine (CPA) has been proposed as a potent antiischemic drug for the central nervous system (CNS) [1]. On the othe
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Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate
Journal of controlled release : official journal of the Controlled Release Society, 2015Co-Authors: Giovanna Rassu, Luca Ferraro, Nicola Marchetti, Paolo Giunchedi, Elena Soddu, Massimo Cossu, Antonio Brundu, Guido Cerri, Raymond F. Regan, Elisabetta GaviniAbstract:We propose the formulation and characterization of solid microparticles as Nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine Nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial-like). Nasal Administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) to 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after Nasal Administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD Nasal Administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.
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Solid microparticles based on chitosan or methyl-beta-cyclodextrin: A first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate
'Elsevier BV', 2015Co-Authors: Giovanna Rassu, Paolo Giunchedi, Elena Soddu, Massimo Cossu, Antonio Brundu, Guido Cerri, Marchetti Nicola, Ferraro, Luca Nicola, F. R. Regan, Elisabetta GaviniAbstract:We propose the formulation and characterization of solid microparticles as Nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine Nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron like), but like DCH did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial like). Nasal Administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) and 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after Nasal Administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD Nasal Administration were 6% and 15%, respectively. Chitosan chloride and methy-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure
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new chitosan derivatives for the preparation of rokitamycin loaded microspheres designed for ocular or Nasal Administration
Journal of Pharmaceutical Sciences, 2009Co-Authors: Giovanna Rassu, Elisabetta Gavini, Helene Jonassen, Ylenia Zambito, Stefano Fogli, Maria Cristina Breschi, Paolo GiunchediAbstract:Acanthamoeba spp. are the causative agents of granulomatous amoebic encephalitis (GAE) and amoebic keratitis. Recent studies performed by Rassu et al. showed that, compared with the free drug, the loading of rokitamycin in chitosan microspheres improves and prolongs the in vitro antiamoebic activity of rokitamycin. This could be useful in transporting the drug for either ocular application to treat amoebic keratitis or Nasal Administration as an alternative route for the Administration of the drug to the brain in GAE therapy. Starting from the previous study, our goal was to optimize the technological parameters in order to obtain chitosan microparticles loaded with rokitamycin and to evaluate the use of new quaternary ammonium chitosan derivatives in the preparation of spray dried microspheres containing the macrolide; these derivatives showed better characteristics (solubility, penetration enhancement) compared with chitosan itself. Toxicity studies on new polymers were performed. Spray dried loaded microspheres based on chitosan or chitosan derivatives were obtained by using appropriate preparative parameters. Microparticles containing chitosan derivatives showed similar or often better properties than formulations made of chitosan with respect to size, in vitro release behaviour and mucoadhesiveness thus making them more suitable for ocular or Nasal Administration. New polymers did not demonstrate cytotoxicity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4852–4865, 2009
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Nasal Administration of Drug Loaded Chitosan Microparticles and Brain Uptake
CRS Italy Local Chapter, 2009Co-Authors: Alessandro Dalpiaz, Elisabetta Gavini, Giovanna Rassu, L. Ferraro, Paolo GiunchediAbstract:Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and muco-adhesiveness. The existence of direct pathways from the Nasal cavity to the central nervous system (CNS) raises the possibility that intraNasal drug Administration may allow therapeutics that cannot penetrate the blood brain barrier (BBB) to be rapidly targeted to CNS using olfactory and trigeminal neural pathways. Our recent studies have shown the possibility to deliver directly to CNS an anti-ischemic drug, unable to cross the BBB, by Nasal Administration of microparticulate system prepared by using chitosan hydrochloride. The drug was found in the liquor at concentrations up to two order of magnitude higher than those obtained at systemic level. Based on these results, we have prepared and characterized new chitosan microparticles containing rokitamicin (RK) for Nasal delivery. RK is a semisynthetic macrolide of the leucomycin group currently studied as alternative drug to the analogous macrolide antibiotics and for the treatment of granulomatous amoebic encephalitis caused by Acanthamoeba. The microparticles have been obtained by spray-drying with chitosan or chitosan glutamate. The powders have been investigated for particle size, morphology, in vitro drug release, mucoadhesive properties, and water uptake. In vivo studies were carried out in rats comparing the intravenous and the Nasal Administration of RK: the drug levels in blood and in liquor were followed for predetermined time periods after Nasal Administration of the microparticles. Only the microparticles obtained with chitosan glutamate allowed rokitamcyn to be absorbed in blood-stream and liquor
Elisabetta Gavini - One of the best experts on this subject based on the ideXlab platform.
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BRAIN TARGETING OF AN ANTIISCHEMIC AGENT BY Nasal Administration OF MICROPARTICLES
2015Co-Authors: Ro Dalpiaz, Luca Ferraro, Elisabetta Gavini, Paolo Giunchedi, Gaia Colombo, Fabrizio Bortolotti, Sergio Tanganelli, Angelo Scatturin, Enea Menegatti, Paolo ColomboAbstract:The adenosine derivative N6-cyclopentyladenosine (CPA) has been proposed as a potent antiischemic drug for the central nervous system (CNS) [1]. On the othe
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Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate
Journal of controlled release : official journal of the Controlled Release Society, 2015Co-Authors: Giovanna Rassu, Luca Ferraro, Nicola Marchetti, Paolo Giunchedi, Elena Soddu, Massimo Cossu, Antonio Brundu, Guido Cerri, Raymond F. Regan, Elisabetta GaviniAbstract:We propose the formulation and characterization of solid microparticles as Nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine Nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial-like). Nasal Administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) to 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after Nasal Administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD Nasal Administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.
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Solid microparticles based on chitosan or methyl-beta-cyclodextrin: A first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate
'Elsevier BV', 2015Co-Authors: Giovanna Rassu, Paolo Giunchedi, Elena Soddu, Massimo Cossu, Antonio Brundu, Guido Cerri, Marchetti Nicola, Ferraro, Luca Nicola, F. R. Regan, Elisabetta GaviniAbstract:We propose the formulation and characterization of solid microparticles as Nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine Nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron like), but like DCH did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial like). Nasal Administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) and 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after Nasal Administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD Nasal Administration were 6% and 15%, respectively. Chitosan chloride and methy-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure
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quantitative determination of zolmitriptan in rat blood and cerebrospinal fluid by reversed phase hplc esi ms ms analysis application to in vivo preclinical pharmacokinetic study
Journal of Chromatography B, 2012Co-Authors: Alessandro Dalpiaz, Alberto Cavazzini, Luisa Pasti, Sarah Beggiato, Elisabetta Gavini, Nicola Marchetti, Sitaram P. Velaga, Luca FerraroAbstract:Abstract A fast HPLC–ESI-MS/MS method has been developed and validated for the quantification of the potent and selective antimigraine zolmitriptan in rat blood and cerebrospinal fluid (CSF). The assay has been then applied for in vivo preclinical studies. The analytical determination has been used to obtain pharmacokinetics of zolmitriptan in the two biological matrices after its intravenous or Nasal Administration. Liquid–liquid extraction of zolmitriptan was performed from 100 μL rat blood samples in the presence of N6-cyclopentyladenosine (internal standard) with the employment of ethyl acetate. Calibration standards were prepared by using blood matrix and following the same liquid–liquid extraction procedure. CSF samples were analyzed without any pre-treatment steps and by using an external calibration method in pure water matrix. Chromatographic separation was performed under reversed phase and a gradient elution condition on a C18 packed column (100 × 2.0 mm, 2.5 μm particles diameter). The mobile phase was a mixture between acetonitrile, water and formic acid (0.1% v/v). The applied HPLC–MS/MS method allowed low limits of detection, as calculated from calibration curves, of 6.6 and 24.4 ng/mL for water matrix and rat blood extracts, respectively. Linearity of the calibration curves was established up to 5 μM (1.44 μg/mL), as well as good assay accuracy. The intravenous infusion of 20 μg zolmitriptan to male Sprague-Dawley rats produced blood concentrations ranging from 9.4 ± 0.7 to 1.24 ± 0.07 μg/mL within 10 h, with a terminal half-life of 3.4 ± 0.2 h. The Nasal Administration of a water suspension of 20 μg zolmitriptan produced blood concentrations ranging from 2.92 ± 0.21 to 0.85 ± 0.07 μg/mL within 6 h. One hour after zolmitriptan intravenous infusion or Nasal Administration, its CSF concentrations were 0.0539 ± 0.0016 and 0.0453 ± 0.0012 μg/mL, respectively. This study determined the suitability of the herein proposed method to investigate the pharmacokinetics of zolmitriptan after its Administration by means of novel formulations and, hence, to evaluate the efficacy of innovative nose-to-brain drug delivery in preclinical studies.
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new chitosan derivatives for the preparation of rokitamycin loaded microspheres designed for ocular or Nasal Administration
Journal of Pharmaceutical Sciences, 2009Co-Authors: Giovanna Rassu, Elisabetta Gavini, Helene Jonassen, Ylenia Zambito, Stefano Fogli, Maria Cristina Breschi, Paolo GiunchediAbstract:Acanthamoeba spp. are the causative agents of granulomatous amoebic encephalitis (GAE) and amoebic keratitis. Recent studies performed by Rassu et al. showed that, compared with the free drug, the loading of rokitamycin in chitosan microspheres improves and prolongs the in vitro antiamoebic activity of rokitamycin. This could be useful in transporting the drug for either ocular application to treat amoebic keratitis or Nasal Administration as an alternative route for the Administration of the drug to the brain in GAE therapy. Starting from the previous study, our goal was to optimize the technological parameters in order to obtain chitosan microparticles loaded with rokitamycin and to evaluate the use of new quaternary ammonium chitosan derivatives in the preparation of spray dried microspheres containing the macrolide; these derivatives showed better characteristics (solubility, penetration enhancement) compared with chitosan itself. Toxicity studies on new polymers were performed. Spray dried loaded microspheres based on chitosan or chitosan derivatives were obtained by using appropriate preparative parameters. Microparticles containing chitosan derivatives showed similar or often better properties than formulations made of chitosan with respect to size, in vitro release behaviour and mucoadhesiveness thus making them more suitable for ocular or Nasal Administration. New polymers did not demonstrate cytotoxicity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4852–4865, 2009
Irina Zvereva - One of the best experts on this subject based on the ideXlab platform.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration. Copyright © 2015 John Wiley & Sons, Ltd.
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determination of growth hormone releasing peptides metabolites in human urine after Nasal Administration of ghrp 1 ghrp 2 ghrp 6 hexarelin and ipamorelin
Drug Testing and Analysis, 2015Co-Authors: Ekaterina Semenistaya, Irina Zvereva, Andreas Thomas, Mario Thevis, Grigory Krotov, G M RodchenkovAbstract:Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after Nasal Administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after Administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after Administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after Administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs Administration depends on individual metabolism, drug preparation form and the way of Administration.
