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Fatih M. Uckun - One of the best experts on this subject based on the ideXlab platform.
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subchronic 13 week toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice
Toxicology, 2002Co-Authors: Osmond J Dcruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B6C3F1 and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 μg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (<0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. The spermicidal vanadocene-chelated complex, VDACAC, may be useful as a safe vaginal contraceptive.
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice.
Toxicology, 2002Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B(6)C(3)F(1) and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC(50) value. After 13 weeks of Intravaginal treatment, B(6)C(3)F(1) mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 microg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (
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GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion
AAPS PharmSciTech, 2001Co-Authors: Osmond J. D’cruz, Fatih M. UckunAbstract:In a systematic effort to develop a dual-function Intravaginal spermicide as well as a drug delivery vehicle against sexually transmitted pathogens, a submicron particle size (30–80 nm), lipophilic and spermicidal gel-microemulsion (viz GM-144) containing the pharmaceutical excipients propylene glycol, Captex 300, Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was formulated. GM-144 completely immobilized sperm in human or rabbit semen in less than 30 seconds. Therefore, the in vivo contraceptive potency of Intravaginally applied GM-144 was compared in the standard rabbit model to those of the detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four ovulated New Zealand White rabbits in subgroups of 28 were artificially inseminated with and without Intravaginal Administration of GM-144 or 2% N-9 (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed remarkable contraceptive activity in the rigorous rabbit model. When compared with control, Intravaginal Administration of GM-144 and Gynol II resulted in 75% and 70.8% inhibition of fertility ( P
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice.
Contraception, 2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Abstract Spermicidal organometallic complexes of vanadium(IV) with bis (cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B 6 C 3 F 1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC 50 value. After 13 weeks of Intravaginal treatment, B 6 C 3 F 1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (
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Original research article Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice
2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Spermicidal organometallic complexes of vanadium(IV) with bis(cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B6C3F1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 1 g/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDDTC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. VDDTC may have clinical utility as an active ingredient of non-detergent type, safe, vaginal spermicidal contraceptives. © 2001 Elsevier Science Inc. All rights reserved.
Barbara Waurzyniak - One of the best experts on this subject based on the ideXlab platform.
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subchronic 13 week toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice
Toxicology, 2002Co-Authors: Osmond J Dcruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B6C3F1 and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 μg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (<0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. The spermicidal vanadocene-chelated complex, VDACAC, may be useful as a safe vaginal contraceptive.
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice.
Toxicology, 2002Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B(6)C(3)F(1) and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC(50) value. After 13 weeks of Intravaginal treatment, B(6)C(3)F(1) mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 microg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice.
Contraception, 2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Abstract Spermicidal organometallic complexes of vanadium(IV) with bis (cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B 6 C 3 F 1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC 50 value. After 13 weeks of Intravaginal treatment, B 6 C 3 F 1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (
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Original research article Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice
2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Spermicidal organometallic complexes of vanadium(IV) with bis(cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B6C3F1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 1 g/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDDTC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. VDDTC may have clinical utility as an active ingredient of non-detergent type, safe, vaginal spermicidal contraceptives. © 2001 Elsevier Science Inc. All rights reserved.
Osmond J Dcruz - One of the best experts on this subject based on the ideXlab platform.
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subchronic 13 week toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice
Toxicology, 2002Co-Authors: Osmond J Dcruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B6C3F1 and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 μg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (<0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. The spermicidal vanadocene-chelated complex, VDACAC, may be useful as a safe vaginal contraceptive.
Osmond J. D'cruz - One of the best experts on this subject based on the ideXlab platform.
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene acetylacetonato monotriflate in mice.
Toxicology, 2002Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. In this study, groups of 10 B(6)C(3)F(1) and 20 CD-1 female mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, or 0.25% of a representative vanadocene, vanadocene acetylacetonato monotriflate (VDACAC), five days per week for 13 consecutive weeks. The doses of VDACAC used were nearly 300- to 1250-fold higher than its in vitro spermicidal EC(50) value. After 13 weeks of Intravaginal treatment, B(6)C(3)F(1) mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematological and clinical chemistry profiles. Microscopic examination was performed on hematoxylin- and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Gel-microemulsion (placebo) control and VDACAC dosed female CD-1 mice were mated with untreated males in order to evaluate if VDACAC has any adverse effects on the reproductive outcome. There were no treatment-related mortalities in either study. Mean body weight gain during the dosing period was not reduced by VDACAC treatment. Hemograms or clinical chemistry profiles did not reveal any toxicologically significant changes attributed to VDACAC treatment. No clinically significant dose-dependent changes in absolute and relative organ weights were noted in VDACAC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDACAC dose groups. Vanadium was not incorporated in mouse tissues at levels above 1 microg/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDACAC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>96%) or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDACAC to yield effective spermicidal concentrations (
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Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice.
Contraception, 2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Abstract Spermicidal organometallic complexes of vanadium(IV) with bis (cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B 6 C 3 F 1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC 50 value. After 13 weeks of Intravaginal treatment, B 6 C 3 F 1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (
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Original research article Subchronic (13-week) toxicity studies of Intravaginal Administration of spermicidal vanadocene dithiocarbamate in mice
2001Co-Authors: Osmond J. D'cruz, Barbara Waurzyniak, Fatih M. UckunAbstract:Spermicidal organometallic complexes of vanadium(IV) with bis(cyclopentadienyl) rings or vanadocenes are a new class of experimental contraceptive agents. In a systematic search for vanadocenes with selective spermicidal activity, we identified vanadocene dithiocarbamate (VDDTC) as the most potent and stable spermicidal compound. In this study, groups of 10 B6C3F1 and 20 female CD-1 mice were exposed Intravaginally to a gel-microemulsion containing 0, 0.06, 0.12, and 0.25% VDDTC 5 days per week for 13 consecutive weeks. The doses of VDDTC used were nearly 1250- to 5000-fold higher than its in vitro spermicidal EC50 value. After 13 weeks of Intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, absolute and relative organ weights, and systemic toxicity. Blood was analyzed for hematologic and clinical chemistry parameters. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Vanadium content in tissues was determined by atomic absorption spectroscopy. Placebo control and VDDTC-dosed female CD-1 mice were mated with untreated males to evaluate whether VDDTC has any deleterious effects on the reproductive performance. There were no treatment-related effects on survival and mean body weight and mean body weight gain during the dosing period. The blood chemistry or hemogram profiles did not reveal any toxicologically significant changes that could be attributed to VDDTC treatment. No clinically significant changes in absolute and relative organ weights were noted in VDDTC dose groups. Extensive histopathological examination of tissues revealed no treatment-related abnormalities in any of the three VDDTC dose groups. The vanadium content of all mouse tissue analyzed was 1 g/g. Repeated Intravaginal exposure of CD-1 mice to increasing concentrations of VDDTC for 13 weeks had no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (90%), or pup development. Collectively, these findings demonstrate that repetitive Intravaginal Administration of VDDTC to yield effective spermicidal concentrations (0.1%) in the vagina was not associated with systemic toxicity and did not adversely affect the reproductive performance in mice. VDDTC may have clinical utility as an active ingredient of non-detergent type, safe, vaginal spermicidal contraceptives. © 2001 Elsevier Science Inc. All rights reserved.
Abdelrazik H Abdelrazik - One of the best experts on this subject based on the ideXlab platform.
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novel in situ gelling vaginal sponges of sildenafil citrate based cubosomes for uterine targeting
Drug Delivery, 2018Co-Authors: Heba M Aboud, Amira H Hassan, Adel A Ali, Abdelrazik H AbdelrazikAbstract:Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is concerned with SIL uterine targeting following Intravaginal Administration via optimization of cubosomal in situ gelling sponges (CIS). An emulsification method was employed for preparation of cubosomal dispersions incorporating glyceryl monooleate as a lipid phase and poloxamer 407 as a surfactant with or without polyvinyl alcohol as a stabilizer. Cubosomes were estimated regarding entrapment efficiency (EE%), particle size, and in vitro drug release. Chitosan (2% w/w) was incorporated into the optimum formulation and then lyophilized into small sponges. For the CIS, in vivo histopathological and pharmacokinetic studies were conducted on female Wistar rats and compared with Intravaginal free SIL sponges (FIS) and oral SIL solution. SIL-loaded cubosomes showed EE% ranging between 32.15 and 72.01%, particle size in the range of 150.81-446.02 nm and sustained drug release over 8 h. Histopathological study revealed a significant enlargement in endometrial thickness with congestion and dilatation of endometrial blood vessels in Intravaginal CIS compared to Intravaginal FIS and oral-treated groups. The pharmacokinetic study demonstrated higher AUC0-∞ and Cmax with oral Administration compared to Intravaginal CIS or Intravaginal FIS indicating potential involvement of first uterine pass effect after Intravaginal Administration. Finally, Intravaginal CIS could be considered as a promising platform for SIL uterine targeting with minimized systemic exposure and side effects.