The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Július Brtko - One of the best experts on this subject based on the ideXlab platform.
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Morphology of 1-methyl-1-nitrosourea induced rat mammary tumours after treatment with precursor of phytanic acid or its combination with vitamin D analogue.
Endocrine regulations, 2012Co-Authors: Líska J, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:OBJECTIVE The proposed therapeutical effect of phytol (PHY), a precursor of the phytanic acid (PHYA), on mammary tumours induced with 1-methyl-1-nitrosourea (MNU), was investigated in Sprague-Dawley rats in combination with vitamin D analogue, Seocalcitol (SEO). METHODS Female Sprague-Dawley rats were administered intraperitoneally with MNU (50 mg/kg of body weight) at the 46th and 52th days of age. Controls and MNU animals received propyleneglycol appropriate to their body weight. PHY (MNU + PHY) (500 mg/kg) was administered after tumour detection (approximately in 100th day of the life) three times/week. Combination of PHY with SEO (7 μg/kg per week) was administered to rats after tumour detection (approximately in 100th day of the life) until the 181st day of age. Then the animals were sacrificed, the tumours removed, and fixed in 10% formalin. Haematoxylin and eosine stained sections were evaluated under microscope. RESULTS Tumour invasiveness observed in all groups of animals was ranging from 80 to 90%. Treatment with PHY alone did not inhibit the progression of the MNU induced tumours in the rat breast but it decreased the tumour burden and volume in comparison with MNU treated controls. Decreased tumour burden and volume were induced by combined treatment of PHY with SEO. Malignity and invasivity of carcinomas were not affected. CONCLUSION No redifferentiating effect on mammary tumour cells induced by NMU after treatment with PHY alone or in combination with SEO was observed in rats. SEO alone or in combination with PHY inhibited the progression of MNU induced mammary tumours and also inhibited the increase of tumour burden and volume in comparison with MNU treated control group. However, none of the compounds, either alone or in mutual combination, reduced the malignity or the number of invasive tumours in this experimental study.
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MNU-induced mammary gland carcinogenesis: chemopreventive and therapeutic effects of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways.
Toxicology letters, 2011Co-Authors: Dana Macejová, Slavomíra Ondková, Lucia Jakubikova, A. Mlynarcikova, S. Scsukova, Líska J, Július BrtkoAbstract:Abstract The effects of administration of vitamin D 3 and Seocalcitol on MNU-induced carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated. Administration of both substances in a weekly dose of 7 μg/kg caused prolonged latency of mammary gland tumors. The latency of tumors was markedly prolonged for 30–40 days by Seocalcitol. Using PET analysis, reduction in [ 18 F]2-fluoro-2-deoxy- d -glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with vitamin D 3 were detected in MNU-induced tumors, vitamin D 3 reduced expression of 25-hydroxylase (25OHase) ( p p 3 was observed in liver, while in kidney, vitamin D 3 and Seocalcitol induced expression of 24OHase was significant. Our observations indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs in carcinogenesis process.
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Histological evaluation of rat mammary tumours after treatment with retinoic acid analogues — phytol, TTNPB and vitamin D_3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D_3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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histological evaluation of rat mammary tumours after treatment with retinoic acid analogues phytol ttnpb and vitamin d3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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Vitamin D3 affects expression of thyroid hormone receptor alpha and deiodinase activity in liver of MNU-treated Sprague-Dawley rats.
General physiology and biophysics, 2009Co-Authors: Dana Macejová, Slavomíra Ondková, Július BrtkoAbstract:1alpha,25-dihydroxyvitamin D3 and its analogue, Seocalcitol (EB1089), are able to reverse or slow the process of carcinogenesis in experimental models and cell cultures. The aim of this study was to investigate the effect of administration vitamin D or Seocalcitol to female Sprague-Dawley rats with 1-methyl-1-nitrosourea (MNU)-induced carcinogenesis of mammary glands on binding characteristics and mRNA levels of thyroid hormone receptors (TRs). Chemopreventive administration of vitamin D caused significant reduction of animal body weight. The expression of TRalpha mRNA was significantly higher in liver of animals treated with vitamin D after detection of first tumour. In our experiment, administration of vitamin D or Seocalcitol significantly reduced KA (group MNU+Seo; MNU+D) and increased Bmax (group MNU+Seo) of thyroid receptors in liver when compared to healthy animals. We show that the activity type I 5'-deiodinase was significantly decreased in livers of animals treated with vitamin D. The data from our in vivo experiment has clearly shown, for the first time, that vitamin D but not Seocalcitol i) may affect the body weight of animals, ii) can cause an increase in the expression of TRalpha in rat liver, remaining the functionality of the TRs unaffected, and iii) is responsible for type I iodothyronine 5'-deiodinase activity decrease in rat liver, remaining the expression of the enzyme unaffected.
Anette Mullertz - One of the best experts on this subject based on the ideXlab platform.
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Bioavailability of Seocalcitol III. Administration of lipid-based formulations to minipigs in the fasted and fed state.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2007Co-Authors: Mette Grove, Anette Mullertz, Gitte P Pedersen, Jeanet Logsted NielsenAbstract:The bioavailability of Seocalcitol from two lipid-based formulations and a propylene glycol (PG) solution was studied in minipigs in the fasted and fed state. The lipid-based formulations were a medium chain triglyceride (MCT) solution and a self-microemulsifying drug delivery system (MC-SMEDDS) having a composition of 25% MCT, 48% cremophor RH 40, 27% akoline MCM. An IV solution was administered in order to determine the absolute bioavailability. In the fasted state the absolute bioavailability of Seocalcitol was 15, 21 and 28% for the PG, MCT and MC-SMEDDS, respectively. The bioavailability from the PG solution was affected by the presence of food (29%), whereas the bioavailability from the lipid-based formulations was less affected by the presence of food; MCT (22%) and MC-SMEDDS (33%). The increased bioavailability from the PG solution in the fed state is believed to be due to the presence of lipids in the food. The present study illustrates an often mentioned beneficial effect of dosing lipid-based formulations; the reduced food effect on bioavailability. Previously published solubility data in simulated intestinal media relates very well to the present in vivo findings as the solubility studies showed that addition of lipids to the formulation could reduce/eliminate the difference in solubility between the fasted and fed state. Previously the same formulations were dosed to rats, resulting in a lower bioavailability from the MC-SMEDDS compared to the MCT. This illustrates that the animal model used should be carefully considered when studying formulations that are dependent on the dynamic processes in the GIT.
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Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats
Pharmaceutical Research, 2006Co-Authors: Mette Grove, Gitte P Pedersen, Jeanet L. Nielsen, Anette MullertzAbstract:Purpose To study the use of long chain triglycerides (LCT) as a lymphotropic carrier of ^3H-Seocalcitol by comparing the lymphatic transport and the portal absorption of ^3H-Seocalcitol when dissolved in a (1) LCT solution or a (2) reference solution without lipid containing propylene glycol (PG). Materials and Methods A lymph cannulated conscious rat model was dosed orally with ^3H-Seocalcitol dissolved in either LCT or PG. Lymph was collected continuously, and blood was sampled over 9 h. ^3H-Seocalcitol in blood and lymph and triglycerides in lymph were analysed. Results A statistically significantly ( p < 0.05) higher recovery of the dosed ^3H-Seocalcitol was found in the intestinal lymph upon administration of the LCT solution (1.3 ± 0.6%) compared to the PG solution (0.5 ± 0.4%). The portal absorption of ^3H-Seocalcitol was significantly ( p < 0.05) higher from the LCT solution (16.2 ± 2.2%) than from the PG solution (10.8 ± 0.8%). Conclusions The LCT solution resulted in a statistical significantly higher level of lymphatic and portal transport of ^3H-Seocalcitol compared with the PG solution. However, even though LCT facilitates the formation of chylomicrons, ^3H-Seocalcitol favours absorption directly to the portal blood probably due to the moderate lipophilicity of the molecule.
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Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats
Pharmaceutical research, 2006Co-Authors: Mette Grove, Jeanet Logsted Nielsen, Gitte P Pedersen, Anette MullertzAbstract:Purpose To study the use of long chain triglycerides (LCT) as a lymphotropic carrier of 3H-Seocalcitol by comparing the lymphatic transport and the portal absorption of 3H-Seocalcitol when dissolved in a (1) LCT solution or a (2) reference solution without lipid containing propylene glycol (PG).
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bioavailability of Seocalcitol ii development and characterisation of self microemulsifying drug delivery systems smedds for oral administration containing medium and long chain triglycerides
European Journal of Pharmaceutical Sciences, 2006Co-Authors: Mette Grove, Anette Mullertz, Jeanet Logsted Nielsen, Gitte P PedersenAbstract:Abstract By constructing ternary phase diagrams it was possible to identify two self-microemulsifying drug delivery systems (SMEDDS) containing either medium chain triglycerides (MC-SMEDDS) or long chain triglycerides (LC-SMEDDS), with the same ratio between lipid, surfactant and co-surfactant. The SMEDDS ended up having a composition of 25% lipid, 48% surfactant and 27% co-surfactant, MC-SMEDDS: viscoleo, cremophor RH40, akoline MCM and LC-SMEDDS: sesame oil, cremophor RH40, peceol. Upon dilution with water both SMEDDS resulted in clear to bluish transparent microemulsions with a narrow droplet size of 30 nm. The industrial usefulness of the developed SMEDDS was evaluated with regard to bioavailability and chemical stability using the vitamin D analogue, Seocalcitol, as model compound. The absorption and bioavailability of Seocalcitol in rats were approximately 45% and 18%, respectively, from both the MC-SMEDDS and LC-SMEDDS indicating similar in vivo behavior of the two formulations, despite the difference in nature of lipid component. There was no improvement in bioavailability by the use of SMEDDS, compared to the bioavailability achieved from simple MCT and LCT solutions (22–24%) (Grove, M., Pedersen, G.P., Nielsen, J.L., Mullertz, A., 2005. Bioavailability of Seocalcitol. I. Relating solubility in biorelevant media with oral bioavailability in rats-effect of medium and long chain triglycerides. J. Pharm. Sci. 94, 1830–1838.). After 3 months’ storage at accelerated conditions (40 °C/75% RH), a decrease in concentration of Seocalcitol of 10–11% was found in MC-SMEDDS and LC-SMEDDS compared with a degradation of less than 3% for the simple lipid solutions of MCT and LCT. In this study the simple lipid solutions seem to be a better choice compared with the developed SMEDDS due to a slightly higher bioavailability and a better chemical stability of Seocalcitol.
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bioavailability of Seocalcitol i relating solubility in biorelevant media with oral bioavailability in rats effect of medium and long chain triglycerides
Journal of Pharmaceutical Sciences, 2005Co-Authors: Mette Grove, Jeanet Logsted Nielsen, Gitte P Pedersen, Anette MullertzAbstract:Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL) with and without medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) were developed to study the solubility of Seocalcitol. Both MC-LP and LC-LP were studied in order to investigate the influence of fatty acid chain length on the in vitro solubility of Seocalcitol. The same solubility of Seocalcitol was found in media containing either MC-LP or LC-LP. The bioavailability after oral administration of Seocalcitol dissolved in medium chain triglyceride (MCT), long chain triglyceride (LCT), and a reference formulation containing propylene glycol (PG) was studied in vivo in rats. The lipid formulations showed a twofold increase in bioavailability compared with the reference formulation, indicating positive effects of lipids on the bioavailability reflecting a better solubility in the intestine and protection against precipitation of Seocalcitol in the gastro intestinal tract. There was no difference in the in vivo bioavailability of Seocalcitol between the MCT and the LCT solutions, which correlates with the identical in vitro solubility of Seocalcitol in SIM containing MC-LP or LC-LP.
Dana Macejová - One of the best experts on this subject based on the ideXlab platform.
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Morphology of 1-methyl-1-nitrosourea induced rat mammary tumours after treatment with precursor of phytanic acid or its combination with vitamin D analogue.
Endocrine regulations, 2012Co-Authors: Líska J, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:OBJECTIVE The proposed therapeutical effect of phytol (PHY), a precursor of the phytanic acid (PHYA), on mammary tumours induced with 1-methyl-1-nitrosourea (MNU), was investigated in Sprague-Dawley rats in combination with vitamin D analogue, Seocalcitol (SEO). METHODS Female Sprague-Dawley rats were administered intraperitoneally with MNU (50 mg/kg of body weight) at the 46th and 52th days of age. Controls and MNU animals received propyleneglycol appropriate to their body weight. PHY (MNU + PHY) (500 mg/kg) was administered after tumour detection (approximately in 100th day of the life) three times/week. Combination of PHY with SEO (7 μg/kg per week) was administered to rats after tumour detection (approximately in 100th day of the life) until the 181st day of age. Then the animals were sacrificed, the tumours removed, and fixed in 10% formalin. Haematoxylin and eosine stained sections were evaluated under microscope. RESULTS Tumour invasiveness observed in all groups of animals was ranging from 80 to 90%. Treatment with PHY alone did not inhibit the progression of the MNU induced tumours in the rat breast but it decreased the tumour burden and volume in comparison with MNU treated controls. Decreased tumour burden and volume were induced by combined treatment of PHY with SEO. Malignity and invasivity of carcinomas were not affected. CONCLUSION No redifferentiating effect on mammary tumour cells induced by NMU after treatment with PHY alone or in combination with SEO was observed in rats. SEO alone or in combination with PHY inhibited the progression of MNU induced mammary tumours and also inhibited the increase of tumour burden and volume in comparison with MNU treated control group. However, none of the compounds, either alone or in mutual combination, reduced the malignity or the number of invasive tumours in this experimental study.
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MNU-induced mammary gland carcinogenesis: chemopreventive and therapeutic effects of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways.
Toxicology letters, 2011Co-Authors: Dana Macejová, Slavomíra Ondková, Lucia Jakubikova, A. Mlynarcikova, S. Scsukova, Líska J, Július BrtkoAbstract:Abstract The effects of administration of vitamin D 3 and Seocalcitol on MNU-induced carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated. Administration of both substances in a weekly dose of 7 μg/kg caused prolonged latency of mammary gland tumors. The latency of tumors was markedly prolonged for 30–40 days by Seocalcitol. Using PET analysis, reduction in [ 18 F]2-fluoro-2-deoxy- d -glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with vitamin D 3 were detected in MNU-induced tumors, vitamin D 3 reduced expression of 25-hydroxylase (25OHase) ( p p 3 was observed in liver, while in kidney, vitamin D 3 and Seocalcitol induced expression of 24OHase was significant. Our observations indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs in carcinogenesis process.
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Histological evaluation of rat mammary tumours after treatment with retinoic acid analogues — phytol, TTNPB and vitamin D_3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D_3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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histological evaluation of rat mammary tumours after treatment with retinoic acid analogues phytol ttnpb and vitamin d3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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Vitamin D3 affects expression of thyroid hormone receptor alpha and deiodinase activity in liver of MNU-treated Sprague-Dawley rats.
General physiology and biophysics, 2009Co-Authors: Dana Macejová, Slavomíra Ondková, Július BrtkoAbstract:1alpha,25-dihydroxyvitamin D3 and its analogue, Seocalcitol (EB1089), are able to reverse or slow the process of carcinogenesis in experimental models and cell cultures. The aim of this study was to investigate the effect of administration vitamin D or Seocalcitol to female Sprague-Dawley rats with 1-methyl-1-nitrosourea (MNU)-induced carcinogenesis of mammary glands on binding characteristics and mRNA levels of thyroid hormone receptors (TRs). Chemopreventive administration of vitamin D caused significant reduction of animal body weight. The expression of TRalpha mRNA was significantly higher in liver of animals treated with vitamin D after detection of first tumour. In our experiment, administration of vitamin D or Seocalcitol significantly reduced KA (group MNU+Seo; MNU+D) and increased Bmax (group MNU+Seo) of thyroid receptors in liver when compared to healthy animals. We show that the activity type I 5'-deiodinase was significantly decreased in livers of animals treated with vitamin D. The data from our in vivo experiment has clearly shown, for the first time, that vitamin D but not Seocalcitol i) may affect the body weight of animals, ii) can cause an increase in the expression of TRalpha in rat liver, remaining the functionality of the TRs unaffected, and iii) is responsible for type I iodothyronine 5'-deiodinase activity decrease in rat liver, remaining the expression of the enzyme unaffected.
Mette Grove - One of the best experts on this subject based on the ideXlab platform.
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Bioavailability of Seocalcitol III. Administration of lipid-based formulations to minipigs in the fasted and fed state.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2007Co-Authors: Mette Grove, Anette Mullertz, Gitte P Pedersen, Jeanet Logsted NielsenAbstract:The bioavailability of Seocalcitol from two lipid-based formulations and a propylene glycol (PG) solution was studied in minipigs in the fasted and fed state. The lipid-based formulations were a medium chain triglyceride (MCT) solution and a self-microemulsifying drug delivery system (MC-SMEDDS) having a composition of 25% MCT, 48% cremophor RH 40, 27% akoline MCM. An IV solution was administered in order to determine the absolute bioavailability. In the fasted state the absolute bioavailability of Seocalcitol was 15, 21 and 28% for the PG, MCT and MC-SMEDDS, respectively. The bioavailability from the PG solution was affected by the presence of food (29%), whereas the bioavailability from the lipid-based formulations was less affected by the presence of food; MCT (22%) and MC-SMEDDS (33%). The increased bioavailability from the PG solution in the fed state is believed to be due to the presence of lipids in the food. The present study illustrates an often mentioned beneficial effect of dosing lipid-based formulations; the reduced food effect on bioavailability. Previously published solubility data in simulated intestinal media relates very well to the present in vivo findings as the solubility studies showed that addition of lipids to the formulation could reduce/eliminate the difference in solubility between the fasted and fed state. Previously the same formulations were dosed to rats, resulting in a lower bioavailability from the MC-SMEDDS compared to the MCT. This illustrates that the animal model used should be carefully considered when studying formulations that are dependent on the dynamic processes in the GIT.
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Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats
Pharmaceutical Research, 2006Co-Authors: Mette Grove, Gitte P Pedersen, Jeanet L. Nielsen, Anette MullertzAbstract:Purpose To study the use of long chain triglycerides (LCT) as a lymphotropic carrier of ^3H-Seocalcitol by comparing the lymphatic transport and the portal absorption of ^3H-Seocalcitol when dissolved in a (1) LCT solution or a (2) reference solution without lipid containing propylene glycol (PG). Materials and Methods A lymph cannulated conscious rat model was dosed orally with ^3H-Seocalcitol dissolved in either LCT or PG. Lymph was collected continuously, and blood was sampled over 9 h. ^3H-Seocalcitol in blood and lymph and triglycerides in lymph were analysed. Results A statistically significantly ( p < 0.05) higher recovery of the dosed ^3H-Seocalcitol was found in the intestinal lymph upon administration of the LCT solution (1.3 ± 0.6%) compared to the PG solution (0.5 ± 0.4%). The portal absorption of ^3H-Seocalcitol was significantly ( p < 0.05) higher from the LCT solution (16.2 ± 2.2%) than from the PG solution (10.8 ± 0.8%). Conclusions The LCT solution resulted in a statistical significantly higher level of lymphatic and portal transport of ^3H-Seocalcitol compared with the PG solution. However, even though LCT facilitates the formation of chylomicrons, ^3H-Seocalcitol favours absorption directly to the portal blood probably due to the moderate lipophilicity of the molecule.
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Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats
Pharmaceutical research, 2006Co-Authors: Mette Grove, Jeanet Logsted Nielsen, Gitte P Pedersen, Anette MullertzAbstract:Purpose To study the use of long chain triglycerides (LCT) as a lymphotropic carrier of 3H-Seocalcitol by comparing the lymphatic transport and the portal absorption of 3H-Seocalcitol when dissolved in a (1) LCT solution or a (2) reference solution without lipid containing propylene glycol (PG).
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bioavailability of Seocalcitol ii development and characterisation of self microemulsifying drug delivery systems smedds for oral administration containing medium and long chain triglycerides
European Journal of Pharmaceutical Sciences, 2006Co-Authors: Mette Grove, Anette Mullertz, Jeanet Logsted Nielsen, Gitte P PedersenAbstract:Abstract By constructing ternary phase diagrams it was possible to identify two self-microemulsifying drug delivery systems (SMEDDS) containing either medium chain triglycerides (MC-SMEDDS) or long chain triglycerides (LC-SMEDDS), with the same ratio between lipid, surfactant and co-surfactant. The SMEDDS ended up having a composition of 25% lipid, 48% surfactant and 27% co-surfactant, MC-SMEDDS: viscoleo, cremophor RH40, akoline MCM and LC-SMEDDS: sesame oil, cremophor RH40, peceol. Upon dilution with water both SMEDDS resulted in clear to bluish transparent microemulsions with a narrow droplet size of 30 nm. The industrial usefulness of the developed SMEDDS was evaluated with regard to bioavailability and chemical stability using the vitamin D analogue, Seocalcitol, as model compound. The absorption and bioavailability of Seocalcitol in rats were approximately 45% and 18%, respectively, from both the MC-SMEDDS and LC-SMEDDS indicating similar in vivo behavior of the two formulations, despite the difference in nature of lipid component. There was no improvement in bioavailability by the use of SMEDDS, compared to the bioavailability achieved from simple MCT and LCT solutions (22–24%) (Grove, M., Pedersen, G.P., Nielsen, J.L., Mullertz, A., 2005. Bioavailability of Seocalcitol. I. Relating solubility in biorelevant media with oral bioavailability in rats-effect of medium and long chain triglycerides. J. Pharm. Sci. 94, 1830–1838.). After 3 months’ storage at accelerated conditions (40 °C/75% RH), a decrease in concentration of Seocalcitol of 10–11% was found in MC-SMEDDS and LC-SMEDDS compared with a degradation of less than 3% for the simple lipid solutions of MCT and LCT. In this study the simple lipid solutions seem to be a better choice compared with the developed SMEDDS due to a slightly higher bioavailability and a better chemical stability of Seocalcitol.
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bioavailability of Seocalcitol i relating solubility in biorelevant media with oral bioavailability in rats effect of medium and long chain triglycerides
Journal of Pharmaceutical Sciences, 2005Co-Authors: Mette Grove, Jeanet Logsted Nielsen, Gitte P Pedersen, Anette MullertzAbstract:Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL) with and without medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) were developed to study the solubility of Seocalcitol. Both MC-LP and LC-LP were studied in order to investigate the influence of fatty acid chain length on the in vitro solubility of Seocalcitol. The same solubility of Seocalcitol was found in media containing either MC-LP or LC-LP. The bioavailability after oral administration of Seocalcitol dissolved in medium chain triglyceride (MCT), long chain triglyceride (LCT), and a reference formulation containing propylene glycol (PG) was studied in vivo in rats. The lipid formulations showed a twofold increase in bioavailability compared with the reference formulation, indicating positive effects of lipids on the bioavailability reflecting a better solubility in the intestine and protection against precipitation of Seocalcitol in the gastro intestinal tract. There was no difference in the in vivo bioavailability of Seocalcitol between the MCT and the LCT solutions, which correlates with the identical in vitro solubility of Seocalcitol in SIM containing MC-LP or LC-LP.
Slavomíra Ondková - One of the best experts on this subject based on the ideXlab platform.
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Morphology of 1-methyl-1-nitrosourea induced rat mammary tumours after treatment with precursor of phytanic acid or its combination with vitamin D analogue.
Endocrine regulations, 2012Co-Authors: Líska J, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:OBJECTIVE The proposed therapeutical effect of phytol (PHY), a precursor of the phytanic acid (PHYA), on mammary tumours induced with 1-methyl-1-nitrosourea (MNU), was investigated in Sprague-Dawley rats in combination with vitamin D analogue, Seocalcitol (SEO). METHODS Female Sprague-Dawley rats were administered intraperitoneally with MNU (50 mg/kg of body weight) at the 46th and 52th days of age. Controls and MNU animals received propyleneglycol appropriate to their body weight. PHY (MNU + PHY) (500 mg/kg) was administered after tumour detection (approximately in 100th day of the life) three times/week. Combination of PHY with SEO (7 μg/kg per week) was administered to rats after tumour detection (approximately in 100th day of the life) until the 181st day of age. Then the animals were sacrificed, the tumours removed, and fixed in 10% formalin. Haematoxylin and eosine stained sections were evaluated under microscope. RESULTS Tumour invasiveness observed in all groups of animals was ranging from 80 to 90%. Treatment with PHY alone did not inhibit the progression of the MNU induced tumours in the rat breast but it decreased the tumour burden and volume in comparison with MNU treated controls. Decreased tumour burden and volume were induced by combined treatment of PHY with SEO. Malignity and invasivity of carcinomas were not affected. CONCLUSION No redifferentiating effect on mammary tumour cells induced by NMU after treatment with PHY alone or in combination with SEO was observed in rats. SEO alone or in combination with PHY inhibited the progression of MNU induced mammary tumours and also inhibited the increase of tumour burden and volume in comparison with MNU treated control group. However, none of the compounds, either alone or in mutual combination, reduced the malignity or the number of invasive tumours in this experimental study.
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MNU-induced mammary gland carcinogenesis: chemopreventive and therapeutic effects of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways.
Toxicology letters, 2011Co-Authors: Dana Macejová, Slavomíra Ondková, Lucia Jakubikova, A. Mlynarcikova, S. Scsukova, Líska J, Július BrtkoAbstract:Abstract The effects of administration of vitamin D 3 and Seocalcitol on MNU-induced carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated. Administration of both substances in a weekly dose of 7 μg/kg caused prolonged latency of mammary gland tumors. The latency of tumors was markedly prolonged for 30–40 days by Seocalcitol. Using PET analysis, reduction in [ 18 F]2-fluoro-2-deoxy- d -glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with vitamin D 3 were detected in MNU-induced tumors, vitamin D 3 reduced expression of 25-hydroxylase (25OHase) ( p p 3 was observed in liver, while in kidney, vitamin D 3 and Seocalcitol induced expression of 24OHase was significant. Our observations indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs in carcinogenesis process.
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Histological evaluation of rat mammary tumours after treatment with retinoic acid analogues — phytol, TTNPB and vitamin D_3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D_3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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histological evaluation of rat mammary tumours after treatment with retinoic acid analogues phytol ttnpb and vitamin d3 analogue Seocalcitol
Biologia, 2011Co-Authors: Ján Líška, Slavomíra Ondková, Dana Macejová, Július BrtkoAbstract:The effects of retinoic acid analogue — phytol (precursor of retinoic X receptors ligand), TTNPB (retinoic acid receptor agonist) and Seocalcitol (EB1089, analogue of vitamin D3) in mammary tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU) were investigated. Treatment with phytol, TTNPB and Seocalcitol may have some protective and therapeutical effects on malignant processes. Treatment with these components in combination of TTNPB and phytol or Seocalcitol and phytol inhibited progression of MNU-induced tumours of the rat mammary gland, and also induced decrease of tumour burden and volume in comparison with treated control group. Treatment of rats with the above compounds had no effect on malignity and invasiveness of carcinomas.
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Vitamin D3 affects expression of thyroid hormone receptor alpha and deiodinase activity in liver of MNU-treated Sprague-Dawley rats.
General physiology and biophysics, 2009Co-Authors: Dana Macejová, Slavomíra Ondková, Július BrtkoAbstract:1alpha,25-dihydroxyvitamin D3 and its analogue, Seocalcitol (EB1089), are able to reverse or slow the process of carcinogenesis in experimental models and cell cultures. The aim of this study was to investigate the effect of administration vitamin D or Seocalcitol to female Sprague-Dawley rats with 1-methyl-1-nitrosourea (MNU)-induced carcinogenesis of mammary glands on binding characteristics and mRNA levels of thyroid hormone receptors (TRs). Chemopreventive administration of vitamin D caused significant reduction of animal body weight. The expression of TRalpha mRNA was significantly higher in liver of animals treated with vitamin D after detection of first tumour. In our experiment, administration of vitamin D or Seocalcitol significantly reduced KA (group MNU+Seo; MNU+D) and increased Bmax (group MNU+Seo) of thyroid receptors in liver when compared to healthy animals. We show that the activity type I 5'-deiodinase was significantly decreased in livers of animals treated with vitamin D. The data from our in vivo experiment has clearly shown, for the first time, that vitamin D but not Seocalcitol i) may affect the body weight of animals, ii) can cause an increase in the expression of TRalpha in rat liver, remaining the functionality of the TRs unaffected, and iii) is responsible for type I iodothyronine 5'-deiodinase activity decrease in rat liver, remaining the expression of the enzyme unaffected.
