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Chemical Research in Toxicology Jun 2021Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive... (Review)
Review
Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive organs and the contact between the eyes and GFNs in eye drops, contact lenses, intraocular drug delivery systems and biosensors and even the workers handling these nanomaterials is inevitable, it is necessary to investigate their ocular toxicities and physiological interactions with cells as well as their toxicity mechanisms. The toxicity of GFNs can be extremely affected by their physicochemical properties, including composition, size, surface chemistry, and oxidation level as well as dose and the time of exposure. Up to now, there are several studies on the and toxicity of GFNs; however, a comprehensive review on ocular toxicity and applications of GFNs is missing, and a knowledge about the health risks of eye exposure to the GFNs is predominantly unspecified. This review highlights the ocular applications of GFNs and systematically covers the most recent advances of GFNs' physicochemical properties, and ocular toxicity, and the possible toxicity mechanisms as well as provides some perspectives on the potential risks of GFNs in material development and biomedical applications.
Topics: Eye; Graphite; Humans; Nanostructures; Ophthalmic Solutions
PubMed: 34041903
DOI: 10.1021/acs.chemrestox.0c00340 -
Drug Discovery Today Aug 2019Delivering therapeutics to the eye is challenging on multiple levels: rapid clearance of eyedrops from the ocular surface requires frequent instillation, which is... (Review)
Review
Delivering therapeutics to the eye is challenging on multiple levels: rapid clearance of eyedrops from the ocular surface requires frequent instillation, which is difficult for patients; transport of drugs across the blood-retinal barrier when drugs are administered systemically, and the cornea when drugs are administered topically, is difficult to achieve; limited drug penetration to the back of the eye owing to the cornea, conjunctiva, sclera and vitreous barriers. Nanomedicine offers many advantages over conventional ophthalmic medications for effective ocular drug delivery because nanomedicine can increase the therapeutic index by overcoming ocular barriers, improving drug-release profiles and reducing potential drug toxicity. In this review, we highlight the therapeutic implications of nanomedicine for ocular drug delivery.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Eye; Humans; Nanomedicine; Ophthalmic Solutions
PubMed: 31102733
DOI: 10.1016/j.drudis.2019.05.006 -
Archives of Disease in Childhood Apr 2020To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care.
OBJECTIVE
To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care.
DESIGN
PTX and drug solutions were combined in glass vials, inspected for physical incompatibility and evaluated on the basis of PTX concentrations for chemical compatibility.
RESULTS
No precipitation, colour change or turbidity was observed in any of the test mixtures. The PTX concentration was approximately 5.5% lower when combined with undiluted calcium gluconate injection (100 mg/mL). The PTX concentration ratios for all other combinations, including diluted calcium gluconate injection (50 mg/mL), were in the range of 99.5%-102%.
CONCLUSION
In simulated Y-site conditions, PTX was found to be compatible with 15 parenteral medications and six total parenteral nutrition solutions. Based on PTX concentration tests, it would be prudent to avoid mixing PTX with undiluted calcium gluconate injection.
Topics: Chemical Phenomena; Fat Emulsions, Intravenous; Humans; Infusions, Intravenous; Intensive Care, Neonatal; Parenteral Nutrition; Pentoxifylline; Pharmaceutical Preparations; Pharmaceutical Solutions; Vasodilator Agents
PubMed: 31871042
DOI: 10.1136/archdischild-2019-317912 -
Indian Journal of Ophthalmology May 2024
Topics: Humans; Drug Labeling; Presbyopia; Ophthalmic Solutions
PubMed: 38648444
DOI: 10.4103/IJO.IJO_1476_23 -
International Journal of Nanomedicine 2024Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including... (Review)
Review
Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.
Topics: Humans; Cataract; Nanomedicine; Drug Delivery Systems; Nanoparticles; Animals; Lens, Crystalline; Cataract Extraction; Nanoparticle Drug Delivery System; Ophthalmic Solutions
PubMed: 38736657
DOI: 10.2147/IJN.S463679 -
Journal of Healthcare Engineering 2021In order to evaluate the stability of neonatal parenteral nutrition solution, in this paper, the prescription of neonatal parenteral nutrition solution was investigated...
In order to evaluate the stability of neonatal parenteral nutrition solution, in this paper, the prescription of neonatal parenteral nutrition solution was investigated and analyzed. The formula of neonatal parenteral nutrition solution used, particularly the one utilized in this study, is commonly used in clinical practice. All the neonatal parenteral nutrition solution required for the test was prepared on the purification workbench in a sterile environment. The time points of stability of parenteral nutrient solution were 0, 12, and 24 hours, respectively, and three parallel samples were taken at each time point. Likewise, to investigate the stability of two kinds of fat milk injection in parenteral nutrition solution of neonates and provide a reference for subsequent experiments and to investigate the influence of electrolyte, amino acid, temperature, pH value, mixing sequence, and the final concentration of glucose on the stability of neonatal parenteral nutrition solution, the stability indexes of neonatal parenteral nutrition liquid mainly include appearance, pH, insoluble particles, fat milk particle size, and particle size distribution. Neonatal parenteral nutrition solution prescriptions from the First Affiliated Hospital of Jinan University, specifically from January to June 2019, were collected and statistically processed. The experimental data were processed by SPSS 19.0 software and data mining technology. The results were expressed as mean ± standard deviation and statistically processed by ANOVA. < 0.05 was considered statistically significant. The results showed that the stability of neonatal parenteral nutrient solution was influenced by many factors. The formula of neonatal parenteral nutrition solution is generally reasonable, but there are unreasonable phenomena which are needed to be improved further if feasible.
Topics: Amino Acids; Data Mining; Humans; Infant, Newborn; Parenteral Nutrition; Parenteral Nutrition Solutions; Prescriptions
PubMed: 34900196
DOI: 10.1155/2021/5744656 -
Journal of Managed Care & Specialty... Jan 2023Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative...
Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (varenicline solution) nasal spray and lifitegrast 5% ophthalmic solution for the treatment of dry eye disease.
Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes. To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% ophthalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis. Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 trials of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmer's test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets' variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to calculate the same values for lifitegrast in the XIIDRA New Drug Application and was then compared. LS mean EDS (based on a 100- point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks. Data from 511 subjects (n = 260 treated; 251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were analyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 ( < 0.0001 for all comparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 ( < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 ( < 0.0001). This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology. D White is a consultant for Oyster Point Pharma, Inc. L Hendrix, M Macsai, and A Gibson are employees and shareholders for Oyster Point Pharma, Inc. L Sun was an employee of COEUS, Clinical Research at the time of study conduct and received funding from Oyster Point Pharma, Inc. I Tam is an employee of COEUS, Clinical Research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc was involved in the study design, data collection, data analysis, and preparation of the manuscript and is the manufacturer/licensee of OC-01 (varenicline solution) nasal spray. Oyster Point Pharma, Inc., sponsored the phase 3 OC-01 (varenicline solution) clinical study from which analysis data were obtained.
Topics: Humans; Data Collection; Dry Eye Syndromes; Nasal Sprays; Ophthalmic Solutions; Treatment Outcome; Varenicline
PubMed: 36030415
DOI: 10.18553/jmcp.2022.22208 -
PloS One 2022To evaluate the concentrations of brimonidine and timolol in the vitreous and aqueous humors after instillation of a 0.1% brimonidine tartrate and 0.5% timolol... (Clinical Trial)
Clinical Trial
Brimonidine and timolol concentrations in the human vitreous and aqueous humors after topical instillation of a 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution: An interventional study.
PURPOSE
To evaluate the concentrations of brimonidine and timolol in the vitreous and aqueous humors after instillation of a 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution.
METHODS
This single-arm open-label interventional study included patients with macular holes or idiopathic epiretinal membranes who were scheduled for vitrectomy. Written informed consent was obtained from all participants. A 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution was administered topically twice daily for 1 week preoperatively. The vitreous and aqueous humors were sampled before vitrectomy, and brimonidine and timolol concentrations were quantified using liquid chromatography-tandem spectrometry. This study was registered with the Japan Registry of Clinical Trials (jRCT, ID jRCTs051200008; date of access and registration: April 28, 2020). The study protocol was approved by the University of Fukui Certified Review Board (CRB) and complied with the tenets of the Declaration of Helsinki.
RESULTS
Eight eyes of eight patients (7 phakic eyes and 1 pseudophakic eye) were included in this study. The mean brimonidine concentrations in the vitreous and aqueous humors were 5.04 ± 4.08 nM and 324 ± 172 nM, respectively. Five of the eight patients had brimonidine concentrations >2 nM in the vitreous humor, which is necessary to activate α2 receptors. The mean timolol concentrations in the vitreous and aqueous humors were 65.6 ± 56.0 nM and 3,160 ± 1,570 nM, respectively. Brimonidine concentrations showed significant positive correlations with timolol concentrations in the vitreous humor (P < 0.0001, R2 = 0.97) and aqueous humor (P < 0.0001, R2 = 0.96).
CONCLUSIONS
The majority of patients who received a 0.1% brimonidine tartrate and 0.5% timolol topical fixed-combination ophthalmic solution showed a brimonidine concentration >2 nM in the vitreous humor. Brimonidine and timolol may be distributed in the ocular tissues through an identical pathway after topical instillation.
Topics: Humans; Aqueous Humor; Brimonidine Tartrate; Ophthalmic Solutions; Timolol; Vitreous Body
PubMed: 36454807
DOI: 10.1371/journal.pone.0277313 -
Advanced Drug Delivery Reviews Jul 2023Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and... (Review)
Review
Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and physiological barriers while minimising tissue toxicity has restricted developments in this field. Aqueous vehicles have traditionally been used, which typically require several additives and preservatives to achieve physiologically compatible and sterile eyedrops, elevating their toxicity potential. Non-aqueous vehicles have been suggested as efficient alternatives for topical drug delivery as they can address many of the limitations associated with conventional aqueous eyedrops. However, despite their obvious advantages, non-aqueous eyedrops remain poorly researched and few non-aqueous formulations are currently available in the market. This review challenges the conventional hypothesis that aqueous solubility is a prerequisite to ocular drug absorption and establishes a rationale for using non-aqueous vehicles for ocular drug delivery. Recent advances in the field have been detailed and future research prospects have been explored, pointing towards a paradigm shift in eyedrop formulation in the near future.
Topics: Humans; Administration, Topical; Eye; Drug Delivery Systems; Ophthalmic Solutions
PubMed: 37178927
DOI: 10.1016/j.addr.2023.114867 -
Optometry and Vision Science : Official... Aug 2023Dry eye is a common condition with serious implications worldwide. The unique composition of autologous serum (AS) eye drops has been hypothesized as a possible...
BACKGROUND
Dry eye is a common condition with serious implications worldwide. The unique composition of autologous serum (AS) eye drops has been hypothesized as a possible treatment.
OBJECTIVES
This study aimed to review the effectiveness and safety of AS.
DATA SOURCES
We searched five databases and three registries up to September 30, 2022.
STUDY ELIGIBILITY
We included randomized controlled trials (RCTs) comparing AS with artificial tears, saline, or placebo for participants with dry eye.
STUDY APPRAISAL AND SYNTHESIS METHODS
We adhered to Cochrane methods for study selection, data extraction, risk-of-bias assessment, and synthesis. We used the Grading of Recommendations Assessment, Development and Evaluation framework to evaluate the certainty of evidence.
RESULTS
We included six RCTs with 116 participants. Four trials compared AS with artificial tears. We found low-certainty evidence that AS may improve symptoms (0- to 100-point pain scale) after 2 weeks of treatment compared with saline (mean difference, -12.00; 95% confidence interval, -20.16 to -3.84; 1 RCT, 20 participants). Ocular surface outcomes (corneal staining, conjunctival staining, tear breakup time, Schirmer test) were inconclusive. Two trials compared AS with saline. Very low-certainty evidence suggested that Rose Bengal staining (0- to 9-point scale) may be slightly improved after 4 weeks of treatment compared with saline (mean difference, -0.60; 95% confidence interval, -1.11 to -0.09; 35 eyes). None of the trials reported outcomes of corneal topography, conjunctival biopsy, quality of life, economic outcomes, or adverse events.
LIMITATIONS
We were unable to use all data because of unclear reporting.
CONCLUSIONS
The effectiveness of AS is uncertain based on current data. Symptoms improved slightly with AS compared with artificial tears for 2 weeks. Staining scores improved slightly with AS compared with saline, with no benefit identified for other measures.
IMPLICATIONS OF KEY FINDINGS
High-quality, large trials enrolling diverse participants with varying severity are needed. A core outcome set would allow for evidence-based treatment decisions consistent with current knowledge and patient values.
Topics: Humans; Lubricant Eye Drops; Dry Eye Syndromes; Serum; Tears; Saline Solution
PubMed: 37410855
DOI: 10.1097/OPX.0000000000002042