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Arquivos Brasileiros de Oftalmologia 2012Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological... (Review)
Review
Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.
Topics: Animals; Clinical Trials as Topic; Complement Pathway, Alternative; Humans; Macular Degeneration
PubMed: 22552424
DOI: 10.1590/s0004-27492012000100016 -
Pharmaceuticals (Basel, Switzerland) Jun 2020Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient...
Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)-CONH was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel's microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel's microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy.
PubMed: 32575910
DOI: 10.3390/ph13060126 -
BMC Pharmacology & Toxicology Mar 2020The study aimed to evaluate and compare the leukocyte chemotactic activities of various brimonidine tartrate (BT) eye drop formulations.
BACKGROUND
The study aimed to evaluate and compare the leukocyte chemotactic activities of various brimonidine tartrate (BT) eye drop formulations.
METHODS
A 96-well dot-blot platet using a Boyden-style well was used to study the chemotactic effects of BT ophthalmic preparations. A modification was made to create blind wells where the tested agents were placed. Leukocytes were isolated from the peripheral blood of healthy volunteers. As positive controls, we used diluted drugs, benzalkonium chloride solution (BAK), zymosan-activated serum, and formyl-methionine-leucine-phenylalanine peptides. The negative control in our study was a phosphate-buffered saline solution. For each experimental condition, we measured leukocyte migration through a Millipore membrane. The differences in the mean migration distance between groups were compared using the analysis of variance (ANOVA).
RESULTS
The measured migration distances (in μm ± SD) were 62.14 ± 3.71 for BT 0.2% with BAK (Alcon Laboratories Inc.); 63.61 ± 3.81 for BT 0.2% with BAK (Allergan Inc); 40.36 ± 3.17 for BT 0.15% without BAK; and 41.02 ± 2.17 for BAK alone. The negative controls showed no chemotactic activity, while the positive controls showed the highest neutrophil migration of all experimental conditions. The differences between BT 0.15% without BAK and the other commercial formulations were statistically significant.
CONCLUSION
Commercial ophthalmic preparations of BT 0.2% with BAK 0.005% had higher chemotactic properties than the alternative of a lower concentration of BT and without the preservative BAK. Therefore, the latter should be considered for patients with glaucoma or ocular hypertension in order to minimize iatrogenic ocular inflammation.
Topics: Administration, Topical; Adult; Antihypertensive Agents; Brimonidine Tartrate; Chemotaxis, Leukocyte; Humans; Middle Aged; Neutrophils; Ophthalmic Solutions; Young Adult
PubMed: 32293549
DOI: 10.1186/s40360-020-0401-z -
RSC Advances May 2023The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections. Drug repurposing has several...
The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections. Drug repurposing has several advantages, including lower costs and improved safety compared to developing a new compound. The aim of the current study is to evaluate the repurposed antimicrobial activity of Brimonidine tartrate (BT), a well-known antiglaucoma drug, and to potentiate its antimicrobial effect by using electrospun nanofibrous scaffolds. BT-loaded nanofibers were fabricated in different drug concentrations (1.5, 3, 6, and 9%) the electrospinning technique using two biopolymers (PCL and PVP). Then, the prepared nanofibers were characterized by SEM, XRD, FTIR, swelling ratio, and drug release. Afterward, the antimicrobial activities of the prepared nanofibers were investigated using different methods against several human pathogens and compared to the free BT. The results showed that all nanofibers were prepared successfully with a smooth surface. The diameters of nanofibers were reduced after loading of BT compared to the unloaded ones. In addition, scaffolds showed controlled-drug release profiles that were maintained for more than 7 days. The antimicrobial assessments revealed good activities for all scaffolds against most of the investigated human pathogens, particularly the one prepared with 9% BT which showed superiority in the antimicrobial effect over other scaffolds. To conclude, our findings proved the capability of nanofibers in loading BT and improving its repurposed antimicrobial efficacy. Therefore, it could be a promising carrier for BT to be used in combating numerous human pathogens.
PubMed: 37200698
DOI: 10.1039/d3ra02244g -
International Journal of Pharmaceutical... Jul 2014Stimuli-sensitive hydrogels are hydrophilic, three-dimensional, polymeric network structure capable of imbibing large amounts of water or biological fluids on...
BACKGROUND
Stimuli-sensitive hydrogels are hydrophilic, three-dimensional, polymeric network structure capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature, and ionic change. Owing to the drawback of conventional therapy for ocular delivery, and to provide additive effect on intraocular pressure (IOP) reduction, stimuli sensitive hydrogel membranes containing a combination of timolol maleate and brimonidine tartrate were formulated for the treatment of glaucoma.
MATERIALS AND METHODS
Stimuli-sensitive hydrogel were formulated by timolol maleate and brimonidine tartrate. Poly acrylic acid (carbopol C 934p) is used as a gelling agent, hydroxylpropyl methylcellulose as viscolizer, sodium chloride as tonicity agent. Bezalkonium chloride as preservative. White rabbits of both sexes, weighing between 2 and 3 kg were used for the study. Stirring of ingredients in pH 4 phosphate buffers at high speed was carried out.
RESULT
Viscosity of the prepared hydrogels lies in the optimum range that is, 25-55 cps. Infrared spectroscopy studies show that there is no interaction between the drug and polymer. Drug released up to 90% at the end of 8 h. The hydrogel membranes were found to be sterile, nonirritant to the eye. Marketed formulation showed a decrease in IOP up to 14 mmHg at the end of 5 h and then elimination of drug, F2 and F6 maintain the sustained effect up to 12 h.
CONCLUSION
Stimuli-sensitive hydrogels was successfully formulated and evaluated for rheological studies, drug release studies, drug interaction studies, sterility studies, ocular irritation studies, and in vivo studies. IOP lowering activity of the combination of timolol maleate and brimonidine tartrate in stimuli-sensitive hydrogel was better when compared with alone medication, which shows the additive effect of combination medication.
PubMed: 25126524
DOI: 10.4103/2230-973X.138340 -
Clinical, Cosmetic and Investigational... 2015Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions....
Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Each subtype stands as a unique entity among a spectrum, with characteristic symptoms and physical findings, along with an intricate pathophysiology. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Topical brimonidine tartrate gel and calcineurin inhibitors are at the forefront of topical therapies, alone or in combination with traditional therapies such as topical metronidazole or azelaic acid and oral tetracyclines or isotretinoin. Vascular laser and intense pulsed light therapies are beneficial for the erythema and telangiectasia, as well as the symptoms (itching, burning, pain, stinging, swelling) of rosacea. Injectable botulinum toxin, topical ivermectin, and microsecond long-pulsed neodymium-yttrium aluminum garnet laser are emerging therapies that may prove to be extremely beneficial in the future. Once a debilitating disorder, rosacea has become a well known and manageable entity in the setting of numerous emerging therapeutic options. Herein, we describe the treatments currently available and give our opinions regarding emerging and combination therapies.
PubMed: 25897253
DOI: 10.2147/CCID.S58940 -
Journal of Young Pharmacists : JYP Oct 2010The objective of the present investigation was to design a vesicular formulation of brimonidine tartrate and evaluate its ability to reduce the dosing frequency and...
The objective of the present investigation was to design a vesicular formulation of brimonidine tartrate and evaluate its ability to reduce the dosing frequency and improve the therapeutic efficacy of the drug. Nano-vesicles of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, and ex-in vitro drug release and in vivo intraocular pressure (IOP) lowering activity. The methods employed for preparation of vesicles produced nano vesicles of acceptable shape and size. The in vitro, and ex-in vitro drug release studies showed that there was slow and prolonged release of the drug, which followed zero-order kinetics. The IOP-lowering activity of nano vesicles was determined and compared with that of pure drug solution and showed that the IOP-lowering action of nano-vesicles sustained for a longer period of time. Stability studies revealed that the vesicle formulations were stable at the temperature range of 2-8°C, with no change in shape and drug content. The results of the study indicate that it is possible to develop a safe and physiologically effective topical formulation that is also convenient for patients.
PubMed: 21264093
DOI: 10.4103/0975-1483.71623 -
Equine Veterinary Journal Nov 2017Brimonidine is an α -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or...
BACKGROUND
Brimonidine is an α -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes.
OBJECTIVES
To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes.
STUDY DESIGN
A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first).
METHODS
Pupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS).
RESULTS
There were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important.
MAIN LIMITATIONS
Horses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma.
CONCLUSIONS
Brimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP.
Topics: Aging; Animals; Brimonidine Tartrate; Brimonidine Tartrate, Timolol Maleate Drug Combination; Circadian Rhythm; Female; Horses; Intraocular Pressure; Male; Pupil
PubMed: 28470857
DOI: 10.1111/evj.12695 -
Translational Vision Science &... Feb 2022Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor.... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager.
METHODS
In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements.
RESULTS
Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds.
CONCLUSIONS
Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results.
TRANSLATIONAL RELEVANCE
The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.
Topics: Adult; Blood Flow Velocity; Brimonidine Tartrate; Glaucoma; Humans; Ocular Hypertension; Sulfonamides; Thiazines; Young Adult
PubMed: 35103799
DOI: 10.1167/tvst.11.2.1 -
Indian Journal of Ophthalmology Jun 2003To compare the short-term efficacy and safety of topical latanoprost and brimonidine in Indian eyes. (Clinical Trial)
Clinical Trial Comparative Study
PURPOSE
To compare the short-term efficacy and safety of topical latanoprost and brimonidine in Indian eyes.
MATERIALS AND METHODS
Twenty-eight patients with ocular hypertension, primary open-angle, pseudoexfoliation or pigmentary glaucoma were enrolled. Following baseline measurements, latanoprost was applied topically once daily in the evening for 12-weeks. After a washout period, brimonidine was applied twice daily in all patients for 6 weeks; 16 patients continued for 12 weeks. Patients were examined at 2, 6 and 12 weeks. The primary outcome measure was the difference in mean intra ocular pressure (IOP) reduction at 6 and 12 weeks. The mean diurnal variation of IOP at baseline and at 12 weeks was also compared.
RESULTS
Twenty-six of 28 enrolled patients completed the study. One randomly selected eye of each patient was used for analysis. At 6 weeks, the mean IOP reduction was 11.2 mm Hg (+/- 2.9 mmHg) with latanoprost and 6 mmHg (+/- 3.3 mmHg) with brimonidine. At 12 weeks this was 10.8 mmHg (+/- 2.8 mmHg) and 6.9 mmHg (+/- 3.1 mmHg) respectively. At 6 weeks 85.7% (24) eyes obtained more than 25% reduction in IOP with latanoprost compared to 13 (46.4%) with brimonidine. IOP reduction was maintained with both drugs throughout the study period. Two eyes did not show any response to brimonidine. Latanoprost reduced the diurnal variation of IOP from 5.10 to 2.90 mmHg; brimonidine reduced it from 4.70 to 3.90 mmHg. Conjunctival hyperaemia was present in one patient on latanoprost and three patients on brimonidine. Two patients experienced drowsiness with brimonidine. Neither drug produced side effects necessitating withdrawal from the study.
CONCLUSION
In this short-term study, both latanoprost and brimonidine effectively reduced IOP and stabilised the diurnal curve in Indian eyes. Latanoprost was more effective than brimonidine.
Topics: Adrenergic alpha-Agonists; Adult; Brimonidine Tartrate; Exfoliation Syndrome; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Quinoxalines; Treatment Outcome
PubMed: 12831141
DOI: No ID Found