| 1. |
- Gudmundsdottir, Birna S., et al.
(author)
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gamma-Cyclodextrin Nanoparticle Eye Drops with Dorzolamide : Effect on Intraocular Pressure in Man
- 2014
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In: Journal of Ocular Pharmacology and Therapeutics. - : Mary Ann Liebert Inc. - 1080-7683 .- 1557-7732. ; 30:1, s. 35-41
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Journal article (peer-reviewed)abstract
- Purpose: To test a new drug delivery platform with dorzolamide γ-cyclodextrin (γCD) nanoparticle eye drops for intraocular pressure (IOP) control and safety and compare with Trusopt.® Methods: Self-aggregating γCD nanoparticle eye drops containing 3% dorzolamide were given once a day (QD) and compared with Trusopt given three times a day (TID) in a prospective randomized single masked crossover trial over 24 h. Seventeen subjects with IOP over 18 mmHg were recruited. IOP was measured with an Icare Tonometer Pro.® Results: There was no statistically significant difference in the IOP lowering effect of dorzolamide nanoparticle eye drops QD and Trusopt TID. At peak (4 h), the IOP reduction from baseline was 3.8±2.6 mmHg (18%, P<0.05) in the nanoparticle eye drop group and 3.1±3.7 mmHg in the Trusopt group (14%, P<0.05, P=0.97 between groups). At trough (24 h), the IOP reduction was 1.4±2.8 mmHg (6%, P>0.05) in nanoparticle eye drop group and 1.5±2.0 mmHg (7%, P>0.05) in the Trusopt group (P=0.23 between groups). Burning sensation measured on the visual analogue scale (1–100) was less from the nanoparticle eye drops (12±15) than from the Trusopt (37±30), (P=0.0038). Visual acuity and conjunctival hyperemia did not differ between the two groups. Conclusions: Dorzolamide cyclodextrin nanoparticle eye drops QD lower IOP and the effect seems comparable to Trusopt given TID. The nanoparticle eye drops are well tolerated and seem to have a better safety profile than Trusopt.
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| 2. |
- Himawan, Erico, et al.
(author)
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Drug delivery to retinal photoreceptors
- 2019
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In: Drug Discovery Today. - : Elsevier BV. - 1359-6446. ; 24:8, s. 1637-1643
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Research review (peer-reviewed)abstract
- The photoreceptors of the retina are afflicted by diseases that still often lack satisfactory treatment options. Although suitable drugs might be available in some cases, the delivery of these compounds into the eye and across the blood–retinal barrier remains a significant challenge for therapy development. Here, we review the routes of drug administration to the retina and highlight different options for drug delivery to the photoreceptor cells.
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| 3. |
- Jóhannesson, Gauti, 1979-, et al.
(author)
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Can postoperative dexamethasone nanoparticle eye drops replace mitomycin C in trabeculectomy?
- 2020
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In: Acta Ophthalmologica. - : Wiley-Blackwell. - 1755-375X .- 1755-3768. ; 98:6, s. 607-612
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Journal article (peer-reviewed)abstract
- Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively.Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months.Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point.Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.
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| 4. |
- Jóhannesson, Gauti, et al.
(author)
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Dorzolamide cyclodextrin nanoparticle suspension eye drops and trusopt in rabbit
- 2014
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In: Journal of Ocular Pharmacology and Therapeutics. - : Mary Ann Liebert. - 1080-7683 .- 1557-7732. ; 30:6, s. 464-467
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Journal article (peer-reviewed)abstract
- Abstract Purpose: Dorzolamide nanoparticle γ-cyclodextrin eye drops may prolong the effect of dorzolamide on intraocular pressure. We test whether the nanoparticle drops have an irritating or toxic effect on the eye in an in vivo rabbit model. Methods: Eighteen pigmented rabbits were divided into 4 groups receiving dorzolamide nanoparticle γ-cyclodextrin eye drops×1/day or×2/day, Trusopt(®) (dorzolamide HCl)×3/day, and untreated controls that received no drops. The rabbits received treatment for 1 month. After sacrifice, 33 eyes and 25 Harderian glands were evaluated for histopathology in a masked way. Results: Mild inflammation was seen in 19/31 eyes and 13/23 Harderian glands. The difference in inflammation (n=eyes/n=glands)between the γ-cyclodextrin nanoparticle eye drops×1/day (n=5/5),×2/day (n=5/3), Trusopt (n=7/4), or untreated control (n=2/0) groups was nonsignificant in both eyes and glands (P=0.87 and P=0.92) Acute inflammation was seen in 1 Harderian gland that received γ-cyclodextrin nanoparticle eye drops×2/day. The difference in conjunctival injection between the groups was nonsignificant (P=0.30). Conclusions: Dorzolamide γ-cyclodextrin nanoparticle eye drops are no more locally toxic or irritating to the eye than Trusopt.
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| 5. |
- Jóhannesson, Gauti, et al.
(author)
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Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid
- 2014
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In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:6, s. 550-556
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Journal article (peer-reviewed)abstract
- PURPOSE: We have developed nanoparticle γ-cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.METHODS: Concentration of dexamethasone was measured by mass spectrometry. One drop of DexNP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time-points after drop instillation. Control eyes received Maxidex(®) (dexamethasone). The same procedure was performed for dorzolamide with DorzNP and Trusopt(®) .RESULTS: Six subjects were included in each group. The peak concentration (μg/ml ± standard deviation) of dexamethasone for DexNP eye drops (636.6 ± 399.1) was up to 19-fold higher than with Maxidex(®) (39.3 ± 18.9) (p < 0.001). At 4 hr, DexNP was still 10 times higher than Maxidex(®) . In addition, DexNP resulted in about 30-fold higher concentration of dissolved dexamethasone in the tear fluid of extended time period allowing more drug to partition into the eye tissue. The overall concentration of dorzolamide was about 50% higher for DorzNP (59.5 ± 76.9) than Trusopt(®) (40.0 ± 76.7) (p < 0.05).CONCLUSION: The results indicate high and extended concentration of dissolved dexamethasone with DexNP, which can explain the greater and longer lasting effect of dexamethasone in the cyclodextrin nanoparticle drug delivery platform. Dexamethasone seems to fit the cyclodextrin nanoparticle suspension drug delivery platform with longer duration and higher concentrations in tear fluid than available commercial drops, while dorzolamide is less suitable.
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| 6. |
- Jóhannesson, Gauti, et al.
(author)
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Microspheres and Nanotechnology for Drug Delivery
- 2016
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In: Developments in ophthalmology. - : S. Karger AG. - 1662-2790. ; 55, s. 93-103
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Journal article (peer-reviewed)abstract
- Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.
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| 7. |
- Ohira, Akihiro, et al.
(author)
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Topical dexamethasone -cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema
- 2015
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In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:7, s. 610-615
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Journal article (peer-reviewed)abstract
- PurposeTo compare in a randomized, controlled trial topical 1.5% dexamethasone -cyclodextrin nanoparticle eye drops (DexNP) with posterior subtenon injection of triamcinolone acetonide in diabetic macular oedema (DME). MethodsIn this prospective, randomized, controlled trial, 22 eyes of 22 consecutive patients with DME were randomized to (i) topical treatment with DexNP x3/day (4weeks), x2/day (4weeks) and x1/day (4weeks) or (ii) one posterior subtenon injection of 20mg triamcinolone acetonide. Study visits were at baseline and 4, 8, 12 and 16weeks. ResultsThe logMAR (Snellen) visual acuity (meanSD) improved significantly with DexNP from 0.41 +/- 0.3 (Snellen 0.39) to 0.32 +/- 0.25 (0.48) and 0.30 +/- 0.26 (0.50) at 4 and 8weeks, respectively. One-third of the DexNP group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42 +/- 0.28 (0.38) at baseline to 0.32 +/- 0.29 (0.48) at 4w and 0.33 +/- 0.37 (0.47) at 12w. The central macular thickness (CMT) decreased significantly with DexNP from 483 +/- 141m to 384 +/- 142m at 4w and 342 +/- 114m at 8w. For triamcinolone, CMT decreased significantly at all time-points: 494 +/- 94m, 388 +/- 120, 388 +/- 145, 390 +/- 136 and 411 +/- 104m at 0, 4, 8, 12 and 16weeks, respectively. There was a modest increase in intraocular pressure (IOP) at all time-points with DexNP while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments. ConclusionTopical DexNP significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone. A modest increase in IOP was seen with the nanoparticle eye drops, but IOP normalized after the discontinuation of treatment.
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| 8. |
- Ohira, Akihiro, et al.
(author)
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Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema
- 2015
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In: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 56:7
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Journal article (other academic/artistic)abstract
- Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of triamcinolone acetonide.Methods: This was a prospective, randomized controlled trial with 22 eyes in 22 consecutive patients with DME, who were randomized to a) topical treatment with dexNP eye drops x3/day for one month, x2/day the next month and finally x1/day the third month or b) one posterior subtenon injection of 20mg triamcinolone acetonide.Results: The central macular thickness (CMT) decreased significantly with dexNP eye drops from 483±141mm to 384±142 mm at 4 weeks and 342±114 mm at 8 weeks. For triamcinolone, CMT decreased significantly at all time points. Visual acuity (logMAR) improved significantly with dexNP eye drops from 0.41±0.3 (mean±SD) to 0.32±0.25 and 0.30±0.26 at 4 and 8 weeks respectively. One third of the eye drop group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42±0.28 at baseline to 0.32±0.29 at 4 weeks and 0.33±0.37 at 12 weeks. There was a modest increase in IOP at all time points with dexNP eye drops while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments.Conclusions: Topical dexamethasone γ-cyclodextrin nanoparticle eye drops significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone as well as to reports on intravitreal steroid implants and triamcinolone intravitreal injections. A modest increase in IOP was seen with the nanoparticle eye drops but IOP normalized after discontinuation of treatment.
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| 9. |
- Perez, Oswaldo, et al.
(author)
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Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations
- 2023
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In: ChemistryOpen. - : John Wiley and Sons Inc. - 2191-1363. ; 12:12
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Journal article (peer-reviewed)abstract
- In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA-H) and salts of sodium (-Na), calcium (-Ca), ammonium (-NH4), triethylammonium (-TEA), tris(hydroxymethyl)aminomethane (-Tris), benethamine (-Bnet), and benzathine (-BZ) were prepared. Their solid-state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X-ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA-BZ featured the lowest aqueous solubility and hygroscopicity, with 50 μg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X-ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP- conformation at the phosphorus atom.
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| 10. |
- Perez, Oswaldo, et al.
(author)
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Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations
- 2023
-
In: ChemistryOpen. - : Wiley. - 2191-1363. ; 12:12
-
Journal article (peer-reviewed)abstract
- In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA-H) and salts of sodium (-Na), calcium (-Ca), ammonium (-NH4), triethylammonium (-TEA), tris(hydroxymethyl)aminomethane (-Tris), benethamine (-Bnet), and benzathine (-BZ) were prepared. Their solid-state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X-ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA-BZ featured the lowest aqueous solubility and hygroscopicity, with 50 μg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X-ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP- conformation at the phosphorus atom.
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