| 1. |
- Gudmundsdottir, Birna S., et al.
(författare)
-
gamma-Cyclodextrin Nanoparticle Eye Drops with Dorzolamide : Effect on Intraocular Pressure in Man
- 2014
-
Ingår i: Journal of Ocular Pharmacology and Therapeutics. - : Mary Ann Liebert Inc. - 1080-7683 .- 1557-7732. ; 30:1, s. 35-41
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Jóhannesson, Gauti, et al.
(författare)
-
Dorzolamide cyclodextrin nanoparticle suspension eye drops and trusopt in rabbit
- 2014
-
Ingår i: Journal of Ocular Pharmacology and Therapeutics. - : Mary Ann Liebert. - 1080-7683 .- 1557-7732. ; 30:6, s. 464-467
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 3. |
- Jóhannesson, Gauti, et al.
(författare)
-
Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid
- 2014
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:6, s. 550-556
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 4. |
- Ohira, Akihiro, et al.
(författare)
-
Topical dexamethasone -cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema
- 2015
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:7, s. 610-615
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Ohira, Akihiro, et al.
(författare)
-
Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema
- 2015
-
Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 56:7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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.
|
|
| 6. |
- Romano, Luigi, 1994, et al.
(författare)
-
A Classification Method of Road Transport Missions and Applications Using the Operating Cycle Format
- 2022
-
Ingår i: IEEE Access. - : Institute of Electrical and Electronics Engineers Inc.. - 2169-3536. ; 10, s. 73087-73121
-
Tidskriftsartikel (refereegranskat)abstract
- When dealing with customers, original equipment manufacturers (OEMs) classify vehicular usage by resorting to simplified, often colloquial, descriptions that allow for a rough understanding of the operating conditions and the user's needs. In this way, the information retrieved from the customers is exploited to guide their choices in terms of vehicle design and configuration, based on the characteristics of the transport application, labeled using intuitive metrics. However, a common problem in this context is the absence of any formal connection to lower levels of representation that might effectively be used to assess vehicular energy performance in simulation, or for design optimization using mathematical algorithms. Indeed, both processes require more accurate modeling of the surroundings, including exhaustive information about the local road, weather, and traffic conditions. Therefore, starting with a detailed statistical description of the environment, this paper proposes a method for mathematical classification of transport missions and applications within the theoretical framework of the operating cycle (OC). The approach discussed in the paper combines a collection of statistical models structured hierarchically, called a stochastic operating cycle (sOC), with a bird's-eye view description of the operating environment. The latter postulates the existence of different classes, which are representative of the usage and whose definition is based on simple metrics and thresholds expressed mathematically in terms of statistical measures. Algebraic expressions, called operating classes in the paper, are derived analytically for all the stochastic models presented. This establishes a connection between the two levels of representation, enabling to simulate longitudinal vehicle dynamics in virtual environments generated based on the characteristics of the intended application, using log data collected from vehicles and/or information provided by customers. Additionally, the relationships between the two descriptions are formalized using elementary probability operators, allowing for an intuitive characterization of a transport operation. An example is adduced to illustrate a possible application of the proposed method, using six sOCs parametrized from log data collected during real-world missions. The proposed approach may facilitate the interaction between OEMs, customers, and road operators, allowing for planning of maintenance, and optimization of transport missions, components, and configurations using standard procedures and routines.
|
|
