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Jari Koistinaho - One of the best experts on this subject based on the ideXlab platform.
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minocycline a Tetracycline Derivative as a potential protective agent for acute stroke
2014Co-Authors: Jari Koistinaho, Milla KoistinahoAbstract:Minocycline and doxycycline, second-generation Tetracyclines that have superior tissue penetration into the brain and cerebrospinal fluid, were reported to provide neuroprotection in global brain ischemia in 1998. Since then these compounds, especially minocycline has been widely studied in numerous in vivo and in vitro models of chronic and acute brain diseases. While the exact mechanism of minocycline’s neuroprotective effect is not clear, minocycline has been shown to have anti-inflammatory, anti-apoptotic, and anti-oxidative effects. Currently, minocycline is in clinical trials for several indications, including ischemic stroke. Here, we review the mechanisms found to be behind minocycline’s beneficial effect so far in models relevant for stroke. We also discuss the importance of using a wide range of stroke models and addressing the comorbidity and gender issues when evaluating minocycline’s potential for treating patients with acute stroke. The chapter also covers the current status of clinical trials of minocycline for treating ischemic stroke.
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a Tetracycline Derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
2013Co-Authors: Tiina Tikka, Ernd L. Fiebich, Gundars Goldsteins, Riitta Keinäne, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 �M) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 �M glutamate or 100 �M kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1 � (IL-1�) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1�. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1 � also in pur
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minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease
Brain, 2002Co-Authors: Tiina Tikka, Gundars Goldsteins, Nina Vartiainen, Simo S Oja, Peter M Andersen, Stefan L Marklund, Jari KoistinahoAbstract:CSF from patients with motor neurone disease (MND) has been reported to be toxic to cultured primary neurones. We found that CSF from MND patients homozygous for the D90A CuZn-superoxide dismutase (CuZn-SOD) mutation, patients with sporadic MND and patients with familial MND without CuZn-SOD mutations significantly increased apoptosis and reduced phosphorylation of neurofilaments in cultured spinal cord neurones when compared with the effects of CSF from patients with other neurological diseases. Exposure of spinal cord cultures to MND CSF also triggered microglial activation. The toxicity of MND CSF was independent of the presence of the CuZn-SOD mutation, and it did not correlate with gelatinase activity or the presence of immunoglobulin G autoantibodies in the CSF. The concentrations of glutamate, aspartate and glycine in MND CSF were not elevated. Antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptors prevented the toxic CSF-induced neuronal death but not microglial activation, whereas minocycline, a Tetracycline Derivative with anti-inflammatory potential independent of antimicrobial activity, reduced both the apoptotic neuronal death and microglial activation. We conclude that the cytotoxic action of CSF is prevalent in all MND cases and that microglia may mediate the toxicity of CSF by releasing excitotoxicity-enhancing factors.
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minocycline provides neuroprotection against n methyl d aspartate neurotoxicity by inhibiting microglia
Journal of Immunology, 2001Co-Authors: Tiina Tikka, Jari KoistinahoAbstract:Glutamate excitotoxicity to a large extent is mediated through activation of the N -methyl-d-aspartate (NMDA)-gated ion channels in several neurodegenerative diseases and ischemic stroke. Minocycline, a Tetracycline Derivative with antiinflammatory effects, inhibits IL-1β-converting enzyme and inducible nitric oxide synthase up-regulation in animal models of ischemic stroke and Huntington’s disease and is therapeutic in these disease animal models. Here we report that nanomolar concentrations of minocycline protect neurons in mixed spinal cord cultures against NMDA excitotoxicity. NMDA treatment alone induced microglial proliferation, which preceded neuronal death, and administration of extra microglial cells on top of these cultures enhanced the NMDA neurotoxicity. Minocycline inhibited all these responses to NMDA. Minocycline also prevented the NMDA-induced proliferation of microglial cells and the increased release of IL-1β and nitric oxide in pure microglia cultures. Finally, minocycline inhibited the NMDA-induced activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells, and a specific p38 MAPK inhibitor, but not a p44/42 MAPK inhibitor, reduced the NMDA toxicity. Together, these results suggest that microglial activation contributes to NMDA excitotoxicity and that minocycline, a Tetracycline Derivative, represents a potential therapeutic agent for brain diseases.
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minocycline a Tetracycline Derivative is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
The Journal of Neuroscience, 2001Co-Authors: Tiina Tikka, Gundars Goldsteins, Bernd L Fiebich, Riitta Keinanen, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 μm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 μm glutamate or 100 μm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1β (IL-1β) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1β. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1β also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.
Lyanne C Schlichter - One of the best experts on this subject based on the ideXlab platform.
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minocycline protects the blood brain barrier and reduces edema following intracerebral hemorrhage in the rat
Experimental Neurology, 2007Co-Authors: Jason K Wasserman, Lyanne C SchlichterAbstract:Intracerebral hemorrhage (ICH) results from rupture of a blood vessel in the brain. After ICH, the blood-brain barrier (BBB) surrounding the hematoma is disrupted, leading to cerebral edema. In both animals and humans, edema coincides with inflammation, which is characterized by production of pro-inflammatory cytokines, activation of resident brain microglia and migration of peripheral immune cells into the brain. Accordingly, inflammation is an attractive target for reducing edema following ICH. In the present study, BBB damage was assessed by quantifying intact microvessels surrounding the hematoma, monitoring extravasation of IgG and measuring brain water content 3 days after ICH induced by collagenase injection into the rat striatum. In the injured brain, the water content increased in both ipsilateral and contralateral hemispheres compared with the normal brain. Quantitative real-time RT-PCR revealed an up-regulation of inflammatory genes associated with BBB damage; IL1beta, TNFalpha and most notably, MMP-12. Immunostaining showed MMP-12 in damaged microvessels and their subsequent loss from tissue surrounding the hematoma. MMP-12 was also observed for the first time in neurons. Dual-antibody labeling demonstrated that neutrophils were the predominant source of TNFalpha protein. Intraperitoneal injection of the Tetracycline Derivative, minocycline, beginning 6 h after ICH ameliorated the damage by reducing microvessel loss, extravasation of plasma proteins and edema; decreasing TNFalpha and MMP-12 expression; and reducing the numbers of TNFalpha-positive cells and neutrophils in the brain. Thus, minocycline, administered at a clinically relevant time, appears to target the inflammatory processes involved in edema development after ICH.
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neuron death and inflammation in a rat model of intracerebral hemorrhage effects of delayed minocycline treatment
Brain Research, 2007Co-Authors: Jason K Wasserman, Lyanne C SchlichterAbstract:After intracerebral hemorrhage (ICH), blood entry is followed by neuron death and an inflammatory response, but development of pharmacological therapies has been hampered by an inadequate understanding of the spatial and temporal relationship between neuron death and inflammation. Using a rat model of ICH, we first investigated these relationships at 6 h, and 1, 3 and 7 days. At the edge of the hematoma, no degenerating neurons were observed at 6 h; however, dying neurons were present between 1 and 3 days, with peak neuron death occurring at 1 day. This is apparently the first report of ongoing neuron death at the edge of the hematoma during a time window that is appropriate for human therapy. Neuron death was limited to the edge of the hematoma, with no degenerating neurons in the striatum surrounding the hematoma, despite robust and prolonged microglia activation. Importantly, neuron loss at the edge of the hematoma was spatially and temporally associated with accumulation and activation of microglia/macrophages. We then tested the hypothesis that treatment with the Tetracycline Derivative, minocycline, after the hematoma had reached a maximal size, will reduce inflammation and neuron damage. Minocycline injection (45 mg/kg i.v. at 6 h, and i.p. at 24, 48 and 72 h) failed to reduce neuron loss outside the hematoma or striatal tissue loss (assessed at 7 days), despite reducing the number of neutrophils and activated microglia/macrophages. Thus, minocycline does not appear to target the mechanisms responsible for cell death in this model of ICH.
Gundars Goldsteins - One of the best experts on this subject based on the ideXlab platform.
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231 PUBLICATIONS 9,154 CITATIONS SEE PROFILE
2016Co-Authors: See Profile, Gundars Goldsteins, Bernd L Fiebich, Available Bernd, L. FiebichAbstract:Minocycline, a Tetracycline Derivative, is neuroprotective against excitotoxicity by inhibiting activation, proliferation of microgli
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a Tetracycline Derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
2013Co-Authors: Tiina Tikka, Ernd L. Fiebich, Gundars Goldsteins, Riitta Keinäne, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 �M) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 �M glutamate or 100 �M kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1 � (IL-1�) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1�. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1 � also in pur
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minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease
Brain, 2002Co-Authors: Tiina Tikka, Gundars Goldsteins, Nina Vartiainen, Simo S Oja, Peter M Andersen, Stefan L Marklund, Jari KoistinahoAbstract:CSF from patients with motor neurone disease (MND) has been reported to be toxic to cultured primary neurones. We found that CSF from MND patients homozygous for the D90A CuZn-superoxide dismutase (CuZn-SOD) mutation, patients with sporadic MND and patients with familial MND without CuZn-SOD mutations significantly increased apoptosis and reduced phosphorylation of neurofilaments in cultured spinal cord neurones when compared with the effects of CSF from patients with other neurological diseases. Exposure of spinal cord cultures to MND CSF also triggered microglial activation. The toxicity of MND CSF was independent of the presence of the CuZn-SOD mutation, and it did not correlate with gelatinase activity or the presence of immunoglobulin G autoantibodies in the CSF. The concentrations of glutamate, aspartate and glycine in MND CSF were not elevated. Antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptors prevented the toxic CSF-induced neuronal death but not microglial activation, whereas minocycline, a Tetracycline Derivative with anti-inflammatory potential independent of antimicrobial activity, reduced both the apoptotic neuronal death and microglial activation. We conclude that the cytotoxic action of CSF is prevalent in all MND cases and that microglia may mediate the toxicity of CSF by releasing excitotoxicity-enhancing factors.
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minocycline a Tetracycline Derivative is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
The Journal of Neuroscience, 2001Co-Authors: Tiina Tikka, Gundars Goldsteins, Bernd L Fiebich, Riitta Keinanen, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 μm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 μm glutamate or 100 μm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1β (IL-1β) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1β. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1β also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.
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minocycline a Tetracycline Derivative is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
The Journal of Neuroscience, 2001Co-Authors: Tiina Tikka, Gundars Goldsteins, Bernd L Fiebich, Riitta Keinanen, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 μm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 μm glutamate or 100 μm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1β (IL-1β) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1β. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1β also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.
Tiina Tikka - One of the best experts on this subject based on the ideXlab platform.
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a Tetracycline Derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
2013Co-Authors: Tiina Tikka, Ernd L. Fiebich, Gundars Goldsteins, Riitta Keinäne, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 �M) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 �M glutamate or 100 �M kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1 � (IL-1�) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1�. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1 � also in pur
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minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease
Brain, 2002Co-Authors: Tiina Tikka, Gundars Goldsteins, Nina Vartiainen, Simo S Oja, Peter M Andersen, Stefan L Marklund, Jari KoistinahoAbstract:CSF from patients with motor neurone disease (MND) has been reported to be toxic to cultured primary neurones. We found that CSF from MND patients homozygous for the D90A CuZn-superoxide dismutase (CuZn-SOD) mutation, patients with sporadic MND and patients with familial MND without CuZn-SOD mutations significantly increased apoptosis and reduced phosphorylation of neurofilaments in cultured spinal cord neurones when compared with the effects of CSF from patients with other neurological diseases. Exposure of spinal cord cultures to MND CSF also triggered microglial activation. The toxicity of MND CSF was independent of the presence of the CuZn-SOD mutation, and it did not correlate with gelatinase activity or the presence of immunoglobulin G autoantibodies in the CSF. The concentrations of glutamate, aspartate and glycine in MND CSF were not elevated. Antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptors prevented the toxic CSF-induced neuronal death but not microglial activation, whereas minocycline, a Tetracycline Derivative with anti-inflammatory potential independent of antimicrobial activity, reduced both the apoptotic neuronal death and microglial activation. We conclude that the cytotoxic action of CSF is prevalent in all MND cases and that microglia may mediate the toxicity of CSF by releasing excitotoxicity-enhancing factors.
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minocycline provides neuroprotection against n methyl d aspartate neurotoxicity by inhibiting microglia
Journal of Immunology, 2001Co-Authors: Tiina Tikka, Jari KoistinahoAbstract:Glutamate excitotoxicity to a large extent is mediated through activation of the N -methyl-d-aspartate (NMDA)-gated ion channels in several neurodegenerative diseases and ischemic stroke. Minocycline, a Tetracycline Derivative with antiinflammatory effects, inhibits IL-1β-converting enzyme and inducible nitric oxide synthase up-regulation in animal models of ischemic stroke and Huntington’s disease and is therapeutic in these disease animal models. Here we report that nanomolar concentrations of minocycline protect neurons in mixed spinal cord cultures against NMDA excitotoxicity. NMDA treatment alone induced microglial proliferation, which preceded neuronal death, and administration of extra microglial cells on top of these cultures enhanced the NMDA neurotoxicity. Minocycline inhibited all these responses to NMDA. Minocycline also prevented the NMDA-induced proliferation of microglial cells and the increased release of IL-1β and nitric oxide in pure microglia cultures. Finally, minocycline inhibited the NMDA-induced activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells, and a specific p38 MAPK inhibitor, but not a p44/42 MAPK inhibitor, reduced the NMDA toxicity. Together, these results suggest that microglial activation contributes to NMDA excitotoxicity and that minocycline, a Tetracycline Derivative, represents a potential therapeutic agent for brain diseases.
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minocycline a Tetracycline Derivative is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
The Journal of Neuroscience, 2001Co-Authors: Tiina Tikka, Gundars Goldsteins, Bernd L Fiebich, Riitta Keinanen, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 μm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 μm glutamate or 100 μm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1β (IL-1β) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1β. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1β also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.
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minocycline a Tetracycline Derivative is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
The Journal of Neuroscience, 2001Co-Authors: Tiina Tikka, Gundars Goldsteins, Bernd L Fiebich, Riitta Keinanen, Jari KoistinahoAbstract:Minocycline, a semisynthetic Tetracycline Derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 μm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 μm glutamate or 100 μm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1β (IL-1β) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1β. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1β also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.
Isabel M Marrucho - One of the best experts on this subject based on the ideXlab platform.
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synthesis characterization and liposome partition of a novel Tetracycline Derivative using the ionic liquids framework
Journal of Pharmaceutical Sciences, 2013Co-Authors: Filipa Alves, Filipe S Oliveira, Bernd Schroder, Carla Matos, Isabel M MarruchoAbstract:Recently, efforts have been put on the development of new drug formulations using ionic liquid framework. In this work, two different species of abroad-spectrum polyketide antibiotic, Tetracycline, are studied in terms of some important properties for antibiotics such as solubility in water and hydrophilic-hydrophobic balance. Tetracycline was used as cation, whereas docusate, a biocompatible anion, which enables the tailoring of the hydrophilicity of salts, was chosen as the anion. The developed innovative ion pair, Tetracycline docusate, was characterized in terms of its thermal stability, water solubility, octanol-water, and liposome-water partition coefficients, using UV-vis spectrophotometry because of the absorbance of Tetracycline around 270 nm. Egg yolk phosphatidylcholine liposomes were used as cell membrane models, and the interactions of both Tetracycline hydrochloride and Tetracycline docusate with the liposomes were quantified by determination of the partition coefficient using Derivative spectrophotometry. A theoretical model based on simple partition drugs between two different media was used to determine the partition coefficient in liposomes.