The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
William C Stewart - One of the best experts on this subject based on the ideXlab platform.
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brimonidine 0 2 vs Unoprostone 0 15 both added to timolol maleate 0 5 given twice daily to patients with primary open angle glaucoma or ocular hypertension
Eye, 2005Co-Authors: E D Sharpe, Jeanette A Stewart, C J Henry, T K Mundorf, D G Day, J N Jenkins, William C StewartAbstract:Brimonidine 0.2% vs Unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension
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the safety and efficacy of Unoprostone 0 15 versus brimonidine 0 2
Acta Ophthalmologica Scandinavica, 2004Co-Authors: William C Stewart, Jeanette A Stewart, Douglas G Day, Jessica N JenkinsAbstract:. Purpose: To compare the efficacy and safety of Unoprostone versus brimonidine both given twice daily in ocular hypertensive or primary open-angle glaucoma subjects. Methods: After a 1-month washout period a baseline diurnal curve was measured every 2 hours from 08 : 00 hours (trough) to 20 : 00 hours in subjects with a trough intraocular pressure (IOP) and the pressure 24 mmHg. Qualified subjects were randomized to either brimonidine or Unoprostone. After 6 weeks of treatment the period 1 diurnal curve was performed. Subjects were then switched to the opposite treatment for 6 weeks and the period 2 diurnal curve was performed. Results: A total of 33 subjects were included in this study. In the brimonidine-treated group the trough IOP 20.1 ± 2.8 mmHg was reduced from baseline up to 8 hours after dosing. In the Unoprostone-treated group the trough IOP was 19.5 ± 3.0 mmHg, which was statistically equal to that of brimonidine (p = 0.21), was reduced from baseline for 12 hours after dosing. Brimonidine decreased the IOP statistically more than Unoprostone at 10 : 00 and 12 : 00 hours (p < 0.0001 and p = 0.02, respectively), while Unoprostone reduced the IOP more than brimonidine at 18 : 00 and 20 : 00 hours (p = 0.002 and p = 0.05, respectively). Safety levels were similar between groups, but Unoprostone caused more ocular stinging than brimonidine (p = 0.008). Conclusion: This study suggests that twice daily brimonidine demonstrates a statistically greater peak reduction in IOP than Unoprostone. However, Unoprostone, but not brimonidine, decreased IOP over the complete 12-hour daytime dosing cycle.
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timolol 0 5 dorzolamide 2 fixed combination vs timolol maleate 0 5 and Unoprostone 0 15 given twice daily to patients with primary open angle glaucoma or ocular hypertension
American Journal of Ophthalmology, 2003Co-Authors: Douglas G Day, Jeanette A Stewart, Elizabeth D Sharpe, Paul N Schacknow, Martin Wand, Jessica N Leech, William C StewartAbstract:Abstract Objective To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and Unoprostone 0.15% given twice daily. Design Prospective multicenter, randomized, double-masked, crossover comparison study. Methods Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 am , 10:00 am , 4:00 pm , 6:00 pm , and 8:00 pm at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days. Results Thirty-two patients completed this trial. The baseline trough pressure was 24.3 ± 3.0 mm Hg, and the diurnal curve was 23.4 ± 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 ± 4.1 mm Hg and the diurnal curve was 19.6 ± 3.6 mm Hg, whereas timolol and Unoprostone concomitant therapy showed a treatment trough pressure of 20.1 ± 4.5 mm Hg and a diurnal pressure of 19.8 ± 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial. Conclusions This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and Unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.
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comparison of the cardiovascular effects of Unoprostone 0 15 timolol 0 5 and placebo in healthy adults during exercise using a treadmill test
Acta Ophthalmologica Scandinavica, 2002Co-Authors: William C Stewart, Jeanette A Stewart, Steve Crockett, Christine Kubilus, Alison Brown, Naveed ShamsAbstract:. Purpose: To compare the cardiovascular effects of Unoprostone 0.15%, timolol 0.5% and placebo in healthy adults during exercise using a treadmill test. Methods: Thirty subjects aged 18–37 years (mean age = 24.1 years) were randomized to one of six treatment sequences in a three-treatment, three-period crossover study (William's design). Study medication was instilled b.i.d. for 5 days before visits 2, 3, and 4. Between treatments, study medication was washed out for 9–10 days. Each subject underwent a submaximal treadmill test at visits 2 through 4, 15 min after dosing. Results: After 15 min of exercise, average heart rates were 143.1 ± 21.2, 134.5 ± 20.0 and 145.4 ± 20.8 bpm for the Unoprostone, timolol and placebo treatments, respectively. At no timepoint was there a statistically significant difference between the Unoprostone and placebo treatments (p > 0.05). Beginning with the second minute of exercise, timolol produced a greater decrease in heart rate at all timepoints from placebo than Unoprostone (p 0.05). Conclusions: Unlike timolol, Unoprostone 0.15% does not reduce exercise-induced heart rate, indicating a lack of clinical effect on systemic β-adrenergic receptors in young and healthy subjects.
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additive efficacy of Unoprostone isopropyl 0 12 rescula to latanoprost 0 005
American Journal of Ophthalmology, 2001Co-Authors: William C Stewart, Jeanette A Stewart, Elizabeth D Sharpe, Keri T Holmes, Kristen E LathamAbstract:Abstract PURPOSE: To evaluate the safety and efficacy of adding Unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening. METHODS: We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or Unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment. RESULTS: Twenty patients were treated in the placebo group and 21 in the Unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 ± 3.2 and 19.1 ± 2.2 mm Hg, respectively. In the Unoprostone isopropyl group the pressures were 19.4 ± 3.3 and 18.0 ± 1.7 mm Hg ( P = .22 and P = .042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough ( P P = .030) after adding Unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P CONCLUSIONS: This study suggests that Unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.
Nobuhiro Nagai - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic and safety evaluation of a transscleral sustained Unoprostone release device in monkey eyes
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Nobuhiro Nagai, Junichi Kawasaki, Matsuhiko Nishizawa, Hirokazu Kaji, Eri Koyanagi, Shinji Yamada, Saaya Saijo, Toru Nakazawa, Toshiaki AbeAbstract:Purpose We evaluate the ocular tissue distribution and retinal toxicity of Unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. Methods The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation. Results M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed. Conclusions The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.
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Physicochemical and biological characterization of sustained isopropyl Unoprostone-release device made of poly(ethyleneglycol) dimethacrylates
Journal of Materials Science: Materials in Medicine, 2017Co-Authors: Nobuhiro Nagai, Yasuko Izumida, Yoshimasa Yamazaki, Junichi Kawasaki, Hirokazu Kaji, Matsuhiko NishizawaAbstract:Transscleral drug delivery is becoming increasingly popular to manage posterior eye diseases. To evaluate the clinical application of a transscleral, sustained, Unoprostone (UNO)-release device (URD) constructed of photopolymerized tri(ethyleneglycol) dimethacrylate and poly(ethyleneglycol) dimethacrylate, we evaluated physicochemical and biological properties of this device. The URD consists of a drug-impermeable reservoir and a semi-permeable cover. The in vitro release rate of UNO from the URD increased with increasing temperatures from 20 to 45 °C. Scanning electron microscopy and atomic-force microscopy showed that the border between the reservoir and drug formulation was sharply defined but that between the cover and drug was poorly determined, indicating that UNO could permeate only through the cover. For stability tests, the URDs were sterilized with ethylene oxide gas and stored at 40 °C/75% for 3 and 6 months and at 25 °C/60% for 3, 6, 9, 12, 18, and 24 months; UNO content and release rate at 37 °C were then evaluated. There was no significant decrease in either UNO content or release rate after the storage conditions. Cytotoxicity was evaluated by examining the colony formation of Chinese hamster fibroblast V79 cells in a media extract of the URD without UNO. This extract did not affect colony formation of V79 cells, indicating the cytocompatibility of the URD. In conclusion, the URD was physically stable for 24 months and is potentially useful for clinical application. Graphical Abstract
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long term protection of genetically ablated rabbit retinal degeneration by sustained transscleral Unoprostone delivery
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Nobuhiro Nagai, Yasuko Izumida, Matsuhiko Nishizawa, Hirokazu Kaji, Eri Koyanagi, Junjun Liu, Aya Katsuyama, Noriko Osumi, Mineo Kondo, Hiroko TerasakiAbstract:Purpose To evaluate the long-term protective effects of transscleral Unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). Methods The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment. Results The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes. Conclusions In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.
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protective effects of sustained transscleral Unoprostone delivery against retinal degeneration in s334ter rhodopsin mutant rats
Journal of Biomedical Materials Research Part B, 2016Co-Authors: Nobuhiro Nagai, Matsuhiko Nishizawa, Hirokazu Kaji, Yukihiko Mashima, Toru Nakazawa, Satoru Iwata, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Toshiaki AbeAbstract:It has been suggested that Unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO-loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO-loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO-loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase-3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730-1737, 2016.
Jeanette A Stewart - One of the best experts on this subject based on the ideXlab platform.
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brimonidine 0 2 vs Unoprostone 0 15 both added to timolol maleate 0 5 given twice daily to patients with primary open angle glaucoma or ocular hypertension
Eye, 2005Co-Authors: E D Sharpe, Jeanette A Stewart, C J Henry, T K Mundorf, D G Day, J N Jenkins, William C StewartAbstract:Brimonidine 0.2% vs Unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension
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the safety and efficacy of Unoprostone 0 15 versus brimonidine 0 2
Acta Ophthalmologica Scandinavica, 2004Co-Authors: William C Stewart, Jeanette A Stewart, Douglas G Day, Jessica N JenkinsAbstract:. Purpose: To compare the efficacy and safety of Unoprostone versus brimonidine both given twice daily in ocular hypertensive or primary open-angle glaucoma subjects. Methods: After a 1-month washout period a baseline diurnal curve was measured every 2 hours from 08 : 00 hours (trough) to 20 : 00 hours in subjects with a trough intraocular pressure (IOP) and the pressure 24 mmHg. Qualified subjects were randomized to either brimonidine or Unoprostone. After 6 weeks of treatment the period 1 diurnal curve was performed. Subjects were then switched to the opposite treatment for 6 weeks and the period 2 diurnal curve was performed. Results: A total of 33 subjects were included in this study. In the brimonidine-treated group the trough IOP 20.1 ± 2.8 mmHg was reduced from baseline up to 8 hours after dosing. In the Unoprostone-treated group the trough IOP was 19.5 ± 3.0 mmHg, which was statistically equal to that of brimonidine (p = 0.21), was reduced from baseline for 12 hours after dosing. Brimonidine decreased the IOP statistically more than Unoprostone at 10 : 00 and 12 : 00 hours (p < 0.0001 and p = 0.02, respectively), while Unoprostone reduced the IOP more than brimonidine at 18 : 00 and 20 : 00 hours (p = 0.002 and p = 0.05, respectively). Safety levels were similar between groups, but Unoprostone caused more ocular stinging than brimonidine (p = 0.008). Conclusion: This study suggests that twice daily brimonidine demonstrates a statistically greater peak reduction in IOP than Unoprostone. However, Unoprostone, but not brimonidine, decreased IOP over the complete 12-hour daytime dosing cycle.
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timolol 0 5 dorzolamide 2 fixed combination vs timolol maleate 0 5 and Unoprostone 0 15 given twice daily to patients with primary open angle glaucoma or ocular hypertension
American Journal of Ophthalmology, 2003Co-Authors: Douglas G Day, Jeanette A Stewart, Elizabeth D Sharpe, Paul N Schacknow, Martin Wand, Jessica N Leech, William C StewartAbstract:Abstract Objective To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and Unoprostone 0.15% given twice daily. Design Prospective multicenter, randomized, double-masked, crossover comparison study. Methods Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 am , 10:00 am , 4:00 pm , 6:00 pm , and 8:00 pm at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days. Results Thirty-two patients completed this trial. The baseline trough pressure was 24.3 ± 3.0 mm Hg, and the diurnal curve was 23.4 ± 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 ± 4.1 mm Hg and the diurnal curve was 19.6 ± 3.6 mm Hg, whereas timolol and Unoprostone concomitant therapy showed a treatment trough pressure of 20.1 ± 4.5 mm Hg and a diurnal pressure of 19.8 ± 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial. Conclusions This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and Unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.
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comparison of the cardiovascular effects of Unoprostone 0 15 timolol 0 5 and placebo in healthy adults during exercise using a treadmill test
Acta Ophthalmologica Scandinavica, 2002Co-Authors: William C Stewart, Jeanette A Stewart, Steve Crockett, Christine Kubilus, Alison Brown, Naveed ShamsAbstract:. Purpose: To compare the cardiovascular effects of Unoprostone 0.15%, timolol 0.5% and placebo in healthy adults during exercise using a treadmill test. Methods: Thirty subjects aged 18–37 years (mean age = 24.1 years) were randomized to one of six treatment sequences in a three-treatment, three-period crossover study (William's design). Study medication was instilled b.i.d. for 5 days before visits 2, 3, and 4. Between treatments, study medication was washed out for 9–10 days. Each subject underwent a submaximal treadmill test at visits 2 through 4, 15 min after dosing. Results: After 15 min of exercise, average heart rates were 143.1 ± 21.2, 134.5 ± 20.0 and 145.4 ± 20.8 bpm for the Unoprostone, timolol and placebo treatments, respectively. At no timepoint was there a statistically significant difference between the Unoprostone and placebo treatments (p > 0.05). Beginning with the second minute of exercise, timolol produced a greater decrease in heart rate at all timepoints from placebo than Unoprostone (p 0.05). Conclusions: Unlike timolol, Unoprostone 0.15% does not reduce exercise-induced heart rate, indicating a lack of clinical effect on systemic β-adrenergic receptors in young and healthy subjects.
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additive efficacy of Unoprostone isopropyl 0 12 rescula to latanoprost 0 005
American Journal of Ophthalmology, 2001Co-Authors: William C Stewart, Jeanette A Stewart, Elizabeth D Sharpe, Keri T Holmes, Kristen E LathamAbstract:Abstract PURPOSE: To evaluate the safety and efficacy of adding Unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening. METHODS: We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or Unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment. RESULTS: Twenty patients were treated in the placebo group and 21 in the Unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 ± 3.2 and 19.1 ± 2.2 mm Hg, respectively. In the Unoprostone isopropyl group the pressures were 19.4 ± 3.3 and 18.0 ± 1.7 mm Hg ( P = .22 and P = .042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough ( P P = .030) after adding Unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P CONCLUSIONS: This study suggests that Unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.
Matsuhiko Nishizawa - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic and safety evaluation of a transscleral sustained Unoprostone release device in monkey eyes
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Nobuhiro Nagai, Junichi Kawasaki, Matsuhiko Nishizawa, Hirokazu Kaji, Eri Koyanagi, Shinji Yamada, Saaya Saijo, Toru Nakazawa, Toshiaki AbeAbstract:Purpose We evaluate the ocular tissue distribution and retinal toxicity of Unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. Methods The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation. Results M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed. Conclusions The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.
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Physicochemical and biological characterization of sustained isopropyl Unoprostone-release device made of poly(ethyleneglycol) dimethacrylates
Journal of Materials Science: Materials in Medicine, 2017Co-Authors: Nobuhiro Nagai, Yasuko Izumida, Yoshimasa Yamazaki, Junichi Kawasaki, Hirokazu Kaji, Matsuhiko NishizawaAbstract:Transscleral drug delivery is becoming increasingly popular to manage posterior eye diseases. To evaluate the clinical application of a transscleral, sustained, Unoprostone (UNO)-release device (URD) constructed of photopolymerized tri(ethyleneglycol) dimethacrylate and poly(ethyleneglycol) dimethacrylate, we evaluated physicochemical and biological properties of this device. The URD consists of a drug-impermeable reservoir and a semi-permeable cover. The in vitro release rate of UNO from the URD increased with increasing temperatures from 20 to 45 °C. Scanning electron microscopy and atomic-force microscopy showed that the border between the reservoir and drug formulation was sharply defined but that between the cover and drug was poorly determined, indicating that UNO could permeate only through the cover. For stability tests, the URDs were sterilized with ethylene oxide gas and stored at 40 °C/75% for 3 and 6 months and at 25 °C/60% for 3, 6, 9, 12, 18, and 24 months; UNO content and release rate at 37 °C were then evaluated. There was no significant decrease in either UNO content or release rate after the storage conditions. Cytotoxicity was evaluated by examining the colony formation of Chinese hamster fibroblast V79 cells in a media extract of the URD without UNO. This extract did not affect colony formation of V79 cells, indicating the cytocompatibility of the URD. In conclusion, the URD was physically stable for 24 months and is potentially useful for clinical application. Graphical Abstract
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long term protection of genetically ablated rabbit retinal degeneration by sustained transscleral Unoprostone delivery
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Nobuhiro Nagai, Yasuko Izumida, Matsuhiko Nishizawa, Hirokazu Kaji, Eri Koyanagi, Junjun Liu, Aya Katsuyama, Noriko Osumi, Mineo Kondo, Hiroko TerasakiAbstract:Purpose To evaluate the long-term protective effects of transscleral Unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). Methods The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment. Results The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes. Conclusions In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.
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protective effects of sustained transscleral Unoprostone delivery against retinal degeneration in s334ter rhodopsin mutant rats
Journal of Biomedical Materials Research Part B, 2016Co-Authors: Nobuhiro Nagai, Matsuhiko Nishizawa, Hirokazu Kaji, Yukihiko Mashima, Toru Nakazawa, Satoru Iwata, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Toshiaki AbeAbstract:It has been suggested that Unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO-loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO-loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO-loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase-3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730-1737, 2016.
Naveed Shams - One of the best experts on this subject based on the ideXlab platform.
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Unoprostone as adjunctive therapy to timolol a double masked randomised study versus brimonidine and dorzolamide
British Journal of Ophthalmology, 2003Co-Authors: A Hommer, B Kapik, Naveed ShamsAbstract:Aims: To compare the safety and efficacy of Unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension. Methods: This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received Unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy. Results: Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (−2.7 mm Hg, Unoprostone; −2.8 mm Hg, brimonidine; −3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between Unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101). Conclusion: Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, Unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.
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safety of Unoprostone isopropyl 0 15 ophthalmic solution in patients with mild to moderate asthma
Ophthalmologica, 2003Co-Authors: Kulasiri A Gunawardena, Beat Mertz, Nathan Crame, Naveed ShamsAbstract:Purpose: To assess the safety of Unoprostone isopropyl 0.15% ophthalmic solution (UIOS) in patients with mild to moderate asthma. Methods: Randomized, double-mask
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comparison of the cardiovascular effects of Unoprostone 0 15 timolol 0 5 and placebo in healthy adults during exercise using a treadmill test
Acta Ophthalmologica Scandinavica, 2002Co-Authors: William C Stewart, Jeanette A Stewart, Steve Crockett, Christine Kubilus, Alison Brown, Naveed ShamsAbstract:. Purpose: To compare the cardiovascular effects of Unoprostone 0.15%, timolol 0.5% and placebo in healthy adults during exercise using a treadmill test. Methods: Thirty subjects aged 18–37 years (mean age = 24.1 years) were randomized to one of six treatment sequences in a three-treatment, three-period crossover study (William's design). Study medication was instilled b.i.d. for 5 days before visits 2, 3, and 4. Between treatments, study medication was washed out for 9–10 days. Each subject underwent a submaximal treadmill test at visits 2 through 4, 15 min after dosing. Results: After 15 min of exercise, average heart rates were 143.1 ± 21.2, 134.5 ± 20.0 and 145.4 ± 20.8 bpm for the Unoprostone, timolol and placebo treatments, respectively. At no timepoint was there a statistically significant difference between the Unoprostone and placebo treatments (p > 0.05). Beginning with the second minute of exercise, timolol produced a greater decrease in heart rate at all timepoints from placebo than Unoprostone (p 0.05). Conclusions: Unlike timolol, Unoprostone 0.15% does not reduce exercise-induced heart rate, indicating a lack of clinical effect on systemic β-adrenergic receptors in young and healthy subjects.
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a double masked randomized comparison of the efficacy and safety of Unoprostone with timolol and betaxolol in patients with primary open angle glaucoma including pseudoexfoliation glaucoma or ocular hypertension 6 month data
American Journal of Ophthalmology, 2002Co-Authors: Jeanphilippe Nordmann, Natalia C. Yannoulis, Barry M Kapik, Beat Mertz, Christine Schwenninger, Naveed ShamsAbstract:Abstract PURPOSE: A long-term comparison of the ocular hypotensive efficacy and safety of Unoprostone isopropyl 0.15% twice daily with that of timolol maleate 0.5% twice daily and betaxolol HCl 0.5% twice daily. DESIGN: This was a randomized, multicenter, double-masked, active-controlled 24-month clinical trial involving 27 centers in Europe and Israel. METHODS: The study population was composed of patients with primary open-angle glaucoma (including pseudoexfoliation) or ocular hypertension. After washout of antiglaucoma medications, intraocular pressure (IOP) was measured at 0, + 2, + 8, and + 12 hours. Patients were randomized in a 2:1:1 ratio to Unoprostone, timolol, or betaxolol. Patients returned for examinations at 2 and 6 weeks and 3 and 6 months. RESULTS: 556 patients were randomized. Each drug produced a clinically and statistically ( P CONCLUSIONS: Unoprostone provided a clinically significant IOP-lowering effect equivalent to betaxolol but not to timolol. The side effect profile of Unoprostone appears to be comparable to other established IOP-lowering agents.
