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This study aimed at formulating the antiglaucoma agent, Bimatoprost (BMT), into niosomal in situ gel (BMT-ISG) for ocular delivery. Niosomes containing cholesterol/span 60 entrapping BMT were fabricated using a thin-film hydration method. The fabricated niosomes were optimized and characterized for entrapment efficiency (%EE) and size. The optimized BMT-loaded niosomal formulation prepared at a cholesterol/span 60 ratio of 1:2 exhibited the highest entrapment (81.2 ± 1.2%) and a small particle size (167.3 ± 9.1 nm), and they were selected for incorporation into in situ gelling systems (BMT-ISGs) based on Pluronic F127/Pluronic F68. Finally, the in vivo efficiency of the BMT-ISG formulation, in terms of lowering the intraocular pressure (IOP) in normotensive male albino rabbits following ocular administration, was assessed and compared to that of BMT ophthalmic solution. All the formulated BMT-ISGs showed sol–gel transition temperatures ranging from 28.1 °C to 40.5 ± 1.6 °C. In addition, the BMT-ISG formulation sustained in vitro BMT release for up to 24 h. Interestingly, in vivo experiments depicted that topical ocular administration of optimized BMT-ISG formulation elicited a significant decline in IOP, with maximum mean decreases in IOP of 9.7 ± 0.6 mm Hg, compared to BMT aqueous solution (5.8 ± 0.6 mm Hg). Most importantly, no signs of irritation to the rabbit’s eye were observed following topical ocular administration of the optimized BMT-ISG formulation. Collectively, our results suggested that niosomal in situ gels might be a feasible delivery vehicle for topical ocular administration of anti-glaucoma agents, particularly those with poor ocular bioavailability.

ObjectiveTo determine bimatoprost， tafluprost ethyl amide， latanoprost， travoprost and tafluprost in eyelash enhancing cosmetics by establishing a LC-MS/MS method.MethodsThe samples were extracted with a 50% acetonitrile water solution. A salt mixture （4 g NaCl， 1 g MgSO4） was added to the solution to induce phase separation. After centrifugation and filtration， the analysis of five prostaglandin analogs was performed with an Agilent Poroshell 120 PFP-C18 （2.7 μm， 2.1 mm×100 mm） column， using 0.02% formic acid containing 5 mmol·L-1 Acetic acid amine and acetonitrile by gradient elution at a flow rate of 0.5 mL·min-1. The analytes were detected with electrospray ionization source in positive ion mode （ESI+） and multiple reaction monitoring （MRM）， and quantified by external standard curve.ResultsThe results showed that it had a good linearity in the range of locatable ambit of concentration with correlation coefficients （r） larger than 0.999. The detection limit of five prostaglandin analogs （LOD） was 0.000 2‒1.5 μg·g-1. The spiked recoveries were 93.2% to 103.5% with a relative standard deviation （RSD） of 1.2% to 3.4%.ConclusionThe method is simple， rapid and highly sensitive. It is suitable for the determination of five prostaglandin analogs in eyelash enhancing cosmetics.

Prostaglandin analogues (PGAs), including bimatoprost (BIM), are generally the first-line therapy for glaucoma due to their greater efficacy, safety, and convenience of use. Commercial solutions of preservative-free BIM (BIM 0.03% and 0.01%) are already available, although their topical application may result in ocular discomfort. This study aimed to evaluate the in vitro effects of preservative-free BIM 0.03% vs. 0.01% in the human conjunctival epithelial (HCE) cell line. Our results showed that long-term exposure to BIM 0.03% ensues a significant decrease in cell proliferation and viability. Furthermore, these events were associated with cell cycle arrest, apoptosis, and alterations of ΔΨm. BIM 0.01% does not exhibit cytotoxicity, and no negative influence on conjunctival cell growth and viability or mitochondrial activity has been observed. Short-time exposure also demonstrates the ability of BIM 0.03% to trigger reactive oxygen species (ROS) production and mitochondrial hyperpolarisation. An in silico drug network interaction was also performed to explore known and predicted interactions of BIM with proteins potentially involved in mitochondrial membrane potential dissipation. Our findings overall strongly reveal better cellular tolerability of BIM 0.01% vs. BIM 0.03% in HCE cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential intraocular pressure (IOP)‐lowering effects of nitric oxide (NO)‐donating compounds in healthy canine eyes Methods: A total of 79 dogs were divided into 3 groups in a masked, controlled and randomised study. Group N (n = 26) was administered 0.03% nitroglycerin in one eye and vehicle‐control in the other, Group H (n = 26) was administered 0.1% hydralazine in one eye and vehicle‐control in the other, while Group C (n = 27) received vehicle‐control in both eyes (control group). Following eye drop administration, IOP was measured in both eyes at selected times (10–250 min), along with monitoring of heart rate and signs of ocular discomfort. Data was analysed with repeated measures mixed model and one‐way ANOVA Results: IOP was significantly reduced over the 4‐h period with 0.03% nitroglycerin (p < 0.0001) but not 0.1% hydralazine (p = 0.520) when compared to contralateral vehicle‐controlled eyes. IOP was reduced by up to 12% with 0.03% nitroglycerin from 10 to 70 min post‐treatment; however, differences in IOP at individual time points were not statistically significant for either drug (p ≥ 0.133) as compared to contralateral vehicle‐control eyes. No treatment group significantly affected heart rate (compared to Group C), and both treatment groups appeared well tolerated Conclusions: Both compounds were well‐tolerated in healthy dogs. Nitroglycerin mildly reduced IOP in canine eyes, and further investigations are warranted in healthy and diseased states (e.g. glaucoma, ocular hypertension). [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a triple fixed-combination of bimatoprost, brimonidine, and timolol (TFC) in patients with glaucoma or ocular hypertension (OHT) treated with fixed-combination or unfixed brimonidine and timolol therapy (dual-combination therapy). Methods: In this multicenter, open-label, phase 3 study, patients who received 4– 8 weeks of dual-combination therapy twice daily and had an IOP > 18 and < 34 mmHg in at least one eye were switched (at baseline) to treatment with TFC twice daily for 12 weeks. At Weeks 4, 8, and 12 on TFC, IOP was assessed at Hours 0, 2, and 8. Primary efficacy variable: mean diurnal IOP change from baseline in the study eye at Week 12 (modified intent-to-treat [mITT] population). Sensitivity (per-protocol [PP] population) and subgroup (≤ 65 vs > 65 years) analyses were performed. Safety, including adverse events (AEs), was assessed at each visit. Results: Of 126 patients enrolled, 121 and 103 formed the mITT/safety and PP populations, including 109 (90.1%) and 94 (91.3%) who completed the study, respectively. In the mITT/safety population, mean age was 58.6 years. Patients had open-angle glaucoma (51.2%), angle-closure glaucoma with patent iridotomy (36.4%), and/or OHT (13.2%). At Week 12, the mean diurnal change in IOP from dual combination-treated baseline was statistically significant (P< 0.001) with TFC in the mITT (– 3.98 mmHg) and PP (– 4.22 mmHg) populations. Results were similar at all visits, regardless of the age subgroup. The most frequent treatment-related AEs were conjunctival hyperemia (14.0%) and dry eye (4.1%); 5.8% of the patients discontinued treatment due to ocular AEs. Conclusion: TFC offers a beneficial therapeutic alternative for patients with glaucoma or OHT whose IOP is not sufficiently controlled with dual-combination therapy. Safety and efficacy findings support those of published studies of TFC in primary open-angle glaucoma and OHT, despite differences in study designs. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether intravenous administration of paracetamol can prevent postoperative ocular hypertension (POH) in dogs following routine phacoemulsification. Methods: Diabetic and non‐diabetic patients (total 54 dogs) undergoing unilateral or bilateral phacoemulsification were recruited to this placebo‐controlled, prospective study. The control group received 1 ml/kg saline via intravenous infusion while the treatment group received 10 mg/kg paracetamol via intravenous infusion. Infusions were administered 30 min prior to surgery and repeated 12 h following initial administration. All patients received topical latanoprost at the conclusion of surgery. Intraocular pressure (IOP) was measured before premedication (baseline), and at 1 h, 3 h, 5 h and 18 h following extubation. POH was defined as an IOP above 25 mmHg (POH25). In addition, the number of patients with an IOP exceeding 20 mmHg was analyzed (POH20). Results: POH20 occurred in 33 of 54 animals (61.1%), including 19 of 25 animals (76.0%) in the control group and 14 of 29 animals (55.2%) in the treatment group. POH25 occurred in 23 of 44 animals (52.3%), including 13 of 25 animals (52.0%) in the control group and 10 of 29 animals (34.5%) in the treatment group. Paracetamol administration showed a significant positive effect on reducing the incidence of POH20 (p =.048), but not POH25 (p =.221). Conclusions: When comparing groups, treatment with paracetamol showed a statistically significant reduction in the incidence of POH20, although no differences were observed in the incidence of POH25 between groups. Further studies are warranted to explore whether alternative drug regimes or routes of administration can provide enhanced efficacy in the prevention of POH25. [ABSTRACT FROM AUTHOR]

BACKGROUND Laser pretreatment with cosmeceutical topicals is growing in popularity. However, lasers may also enhance the uptake of medical topicals that treat dermatologic conditions, such as vitiligo, alopecia, and cancerous and precancerous lesions. Permeation of these topicals must be quantified to optimize treatment protocols. OBJECTIVE To analyze transdermal uptake of 3 topicals after nonablative fractional 1,550-nm erbium-doped glass or 1,927-nm thulium fiber laser pretreatment. METHODS AND MATERIALS Human donor tissue was pretreated with a nonablative fractional 1,550-nm erbium-doped glass or 1,927-nm thulium fiber laser followed by application of 0.03% bimatoprost, 0.5% 5-fluorouracil, or 5% minoxidil. Permeation and retention were measured over 24 hours (bimatoprost and 5-fluorouracil) or 90 minutes (minoxidil), and uptake was calculated. RESULTS Pretreatment with 1,927-nm thulium laser (500 MTZ/cm²; 5 mJ; 5 W) enhanced uptake and retention of bimatoprost versus untreated control at 24 hours post-treatment. Pretreatment with 1,550-nm erbium-doped glass laser (2,000 MTZ/cm²; 10 mJ; 30 W) enhanced permeation, uptake, and retention of 5-fluorouracil at 24 hours post-treatment and enhanced permeation and uptake of minoxidil at 90 minutes post-treatment. CONCLUSION Nonablative laser pretreatment may enhance topical treatment of dermatologic conditions. Device settings must be optimized to maximize topical permeation while minimizing laser-associated thermal side effects. [ABSTRACT FROM AUTHOR]