Tear Turnover Research Articles

Development and Characterization of In-Situ Gel for Ophthalmic Formulation Containing Acyclovir

Acyclovir is acycloguanosine antiviral which is used in the treatment of herpes simplex keratitis. Acyclovir drops are required to be instilled frequently in the eyes (5 times a day), as they exhibit short precorneal residence time and poor bioavailability due to rapid elimination induced by tear turnover, blinking, and drainage of formulation. Moreover, application of its ointment leads to blurring of vision which results into patient non compliance. It was, therefore, thought worthwhile to develop an in-situ gel formulation using a suitable phase transition polymer to effectively deliver the drug into eyes with sustained and prolonged release and enhanced drug bioavailability leading to effective management of herpes simplex keratitis.

Sustained release of proteins from contact lenses with porous annulus.

Ophthalmic drugs are administered to the front of the eye by eyedrops. The bioavailability of drugs delivered via eye drops is low due to tear turnover. Contact lenses can address some deficiencies of eye drops by sustaining the delivery of drugs, but commercial contact lenses have small pore sizes that cannot load biologics, which are becoming more common for treating ophthalmic diseases. This study aims to investigate novel poly(hydroxyethyl methacrylate) (pHEMA) lenses with transparent center and porous annulus for sustained release of model proteins. A novel hydrogel polymerization process was used to fabricate concentric, porous layer pHEMA hydrogel rods. The hydrogels were lathe cut into contact lenses which were explored for the delivery of proteins and gold nanoparticles. Lenses were characterized by partition coefficient and diffusivity, which was estimated by fitting experimental data to an analytical model. Transmittance measurements were made to compare transparency of porous lens centers to commercial contact lenses. Porous pHEMA lenses consisting of a concentric, porous layer made from 55% water content in precursor were successfully lathe cut into lenses with transparent center and opaque porous annulus. The porous lenses could load large model proteins of bovine serum albumin and human γ-globulin and provide sustained release. The core annular pHEMA contact lenses consisting of an outer annulus of opaque, porous pHEMA and an inner, center layer of clear, nonporous pHEMA can provide sustained delivery of biologics.

In silico evaluation of corneal patch eluting anti-VEGF agents concept

This study introduces a novel approach utilizing a temporary drug-eluting hydrogel corneal patch to prevent neovascularization, alongside a numerical predictive tool for assessing the release and transport kinetics of bevacizumab (BVZ) after the keratoplasty. A key focus was investigating the impact of tear film clearance on the release kinetics and drug transport from the designed corneal patch. The proposed tear drug clearance model incorporates the physiological mechanism of lacrimal flow (tear turnover), distinguishing itself from previous models. Validation against experimental data confirms the model’s robustness, despite limitations such as a 2D axisymmetrical framework and omission of blink frequency and saccadic eye movements potential effects. Analysis highlights the significant influence of lacrimal flow on ocular drug transport, with the corneal patch extending BVZ residence time compared to topical administration. This research sets the stage for exploring multi-layer drug-eluting corneal patches as a promising therapeutic strategy in ocular health.

Formulation of Polymeric Nanoparticles Loading Baricitinib as a Topical Approach in Ocular Application.

Topical ocular drug delivery faces several challenges due to the eye's unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing.

Modelling gravity-driven aqueous humour flow and drug delivery in Descemet’s membrane detachment

Topical medications are common initial treatments for Descemet’s membrane detachment (DMD). It is crucial to understand the aqueous humour (AH) flow and drug transport to facilitate the DMD treatment. This paper presents a mathematical model to analyse AH flow and drug transport in the anterior of the human eye considering gravity orientation effects. Utilizing the finite element method, the model couples AH flow dynamics, temperature-induced buoyancy, and drug transport by convection-diffusion. COMSOL Multiphysics is used to simulate the spatial-temporal distribution of AH and drugs delivery. The findings indicate that the eye positioning influences the directional flow of AH, due to temperature differences, and impacts the delivery of drug concentrations. It is also discovered that eye drops diffuse faster due to tear turnover in the eye yet more eye ointment is delivered as it has a longer contact time in the cornea. By understanding the AH flow and transport process, this proposed model may offer appropriate guidelines for optimizing DMD treatment under various forms of topical drugs and eye positions.

Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage

BackgroundDry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients’ quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration.ResultsA novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of “ocular surface electrostatic adhesion-lysosomal site-directed escape”. In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of “anti-inflammation-antioxidation-mitochondrial function restoration” breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo.ConclusionIn summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

Protein Nanoparticles Laden In situ Gel for Topical Ocular Drug Delivery.

Topical ocular delivery of drugs is most commonly preferred route by the patient and physician for the treatment of ocular diseases. The topical route is always followed with the disadvantages like tear turnover, nasolacrimal drainage, reduction in precorneal residence time, etc</i>. To overcome these hindrances associated with topical ocular route, a novel drug delivery system is used for targeting the drug at a specific site. In the Novel Drug delivery System, protein-based nanoparticles are an attractive class of nanoparticles designed to deliver the drug at targeted site in slow and sustained release manner. They have a size in the range of 1-100 nm. Protein nanoparticles are leading, particularly for the topical ocular delivery like reduction in intra ocular pressure, providing sustained release and targeted drug delivery at the site of its action. Various methods are used for formulation of protein nanoparticles like desolvation, emulsification, complex coacervation, electrospray techniques. The characterization parameters include particle size, surface morphology, drug loading and entrapment efficiency. Protein nanoparticles can also be loaded in to the in situ</i> gel forming polymers for increasing precorneal residence time of nanoparticles. The characterization parameters of in situ</i> gelling systems are gelling time, rheological properties, gel strength. The review mainly describes the use of various proteins in preparation of protein nanoparticles, methods for preparation of protein nanoparticles, polymers used in in situ</i> gelling system and evaluation as well as characterization parameters of protein nanoparticles, in situ</i> gelling systems & patented information related to protein nanoparticles and in situ</i> gelling system for ocular drug delivery.

Towards the development of a biorelevant in vitro method for the prediction of nanoemulsion stability on the ocular surface

Ophthalmic oil-in-water nanoemulsions (NEs) are a complex technological platform, representing an advancement in the treatment of dry eye disease. In addition to enabling the incorporation of poorly soluble active pharmaceutical ingredients (APIs), NEs provide prolonged residence time of APIs and other formulation components and consequent replenishment and stabilization of the compromised tear film. Ophthalmic NEs have been on the market for over 20 years, but considering their complexity, as well as the complex nature of the ocular surface, they are still a poorly understood advanced dosage form. The objective of this study was to develop a biorelevant in vitro method that would be able to predict the behavior of ophthalmic NEs after application. With that goal, NE formulations differing in critical material attributes and critical formulation variables were employed and subjected to simulated tear turnover and blinking. By gradually increasing the complexity of the in vitro method, we were able to detect key parameters influencing NE stability. The undertaken study presents a step forward in the development of in vitro tools that are fundamental to the reliable, cost and time-effective development of innovative and generic topical ophthalmic NEs.

Critical Evaluation of Multifunctional Betaxolol Hydrochloride Nanoformulations for Effective Sustained Intraocular Pressure Reduction.

Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability. We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface. The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy. The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.

Development and optimization of ofloxacin as solid lipid nanoparticles for enhancement of its ocular activity

Ofloxacin (Ofx) is one of the most commonly available ocular antibiotic solutions. Unfortunately, it suffers from rapid tear turnover and therefore requires administration every 4 h or even every hour for serious eye infections; moreover, its solubility is pH-dependent and very low at the pH of corneal fluid (7.2–7.4), and it can form a white crystalline deposit on the cornea. Hence, the aim of this investigation was to load Ofx into solid lipid nanoparticles (SLNs) to address its limitations. SLNs were prepared using hot homogenization followed by ultrasonication techniques at a pH of 7.4. The Box-Behnken design addressed the influence of the formulation factors, namely, the effects of the percentages of Compritol, Gelucire 44/14, and stearylamine on the particle size, zeta potential, entrapment efficiency, percentage of Ofx release after 1 h, and time required to release 50% of the drug. The obtained optimal Ofx-SLN was evaluated for its transcorneal permeation, antimicrobial activity, and amount of Ofx present in the aqueous humor as compared with Ofx aqueous suspension, and commercially available Ofx eye drop. The optimum formulation exhibited a particle size of 34 nm, zeta potential of 22 mV, entrapment efficiency of 82%, Ofx release of 9% after 1 h, and time to release of 50% of the drug of 5 h. It produced a 1.5-fold and 3-fold increase in the cumulative amount permeated and cumulative percentage permeated, respectively, compared with other tested formulations. Furthermore, the optimized Ofx-SLN had a high level over the minimum inhibitory concentration in the aqueous humor of rabbits for longer periods compared with a commercial preparation. These data proved that a once-a-day dose of an Ofx-SLN dispersion would produce the required effects of prolonged transcorneal permeation, enhanced ophthalmic bioavailability, diminished need for recurrent administration.

Nano-formulations: Recent Trends for Ocular Bioavailability Enhancement

Eye is a critical part of the body that is readily available and with damage having direct effects on the life of an individual. Delivery of ocular drugs always remain challenging for healthcare professionals and scientists all over the world due to the challenges that dynamic opthalamic environment provides. These challenges involves different barriers like corneal epithelium, corneal stroma, sclera and other bio-membranes (static barriers), choroidal or conjunctival blood flow, lymphatic clearance, tear turnover (dynamic barriers) and efflux pumps/enzymes(metabolic barriers).Ocular diseases include various diseases affecting different parts of the eye. The eye presents comprehensive perspectives and difficulties in the distribution of medicaments, primarily due to the exceptional ability inherent in this mechanism for drugs to enter the main circulatory system and also for eye barrier limitations. Even if conventional non-invasive and invasive treatments like eye drops, injectable preparations and implantable devices are available but these treatments either have bioavailability issues or serious adverse eye effects. Additionally, the new concept of nanoscience and nano-technology gives new a pathway for treating ocular disease. Different active molecules were engineered to communicate with nano-carriers to pass these eye barriers and interact closely with unique specific eye tissues. This study highlights the latest advances in nano-formulations for ophthalmic diagnosis and provides discussions in the mainstream of opthalamic diseases about the role of nano-formulations in nearby future.&#x0D; Keywords: ocular diseases, nano-technology, static barrier, dynamic barrier, nano-carriers, bioavailability.

Drug Delivery Challenges and Current Progress in Nanocarrier-Based Ocular Therapeutic System.

Drug instillation via a topical route is preferred since it is desirable and convenient due to the noninvasive and easy drug access to different segments of the eye for the treatment of ocular ailments. The low dose, rapid onset of action, low or no toxicity to the local tissues, and constrained systemic outreach are more prevalent in this route. The majority of ophthalmic preparations in the market are available as conventional eye drops, which rendered <5% of a drug instilled in the eye. The poor drug availability in ocular tissue may be attributed to the physiological barriers associated with the cornea, conjunctiva, lachrymal drainage, tear turnover, blood–retinal barrier, enzymatic drug degradation, and reflex action, thus impeding deeper drug penetration in the ocular cavity, including the posterior segment. The static barriers in the eye are composed of the sclera, cornea, retina, and blood–retinal barrier, whereas the dynamic barriers, referred to as the conjunctival and choroidal blood flow, tear dilution, and lymphatic clearance, critically impact the bioavailability of drugs. To circumvent such barriers, the rational design of the ocular therapeutic system indeed required enriching the drug holding time and the deeper permeation of the drug, which overall improve the bioavailability of the drug in the ocular tissue. This review provides a brief insight into the structural components of the eye as well as the therapeutic challenges and current developments in the arena of the ocular therapeutic system, based on novel drug delivery systems such as nanomicelles, nanoparticles (NPs), nanosuspensions, liposomes, in situ gel, dendrimers, contact lenses, implants, and microneedles. These nanotechnology platforms generously evolved to overwhelm the troubles associated with the physiological barriers in the ocular route. The controlled-drug-formulation-based strategic approach has considerable potential to enrich drug concentration in a specific area of the eye.

Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations.

Ophthalmic diseases represent a significant problem as over 2 billion people worldwide suffer from vison impairment and blindness. Eye drops account for around 90% of ophthalmic medications but are limited in success due to poor patient compliance and low bioavailability. Low bioavailability can be attributed to short retention times in the eye caused by rapid tear turnover and the difficulty of drug diffusion through the multi-layered structure of the eye that includes lipid-rich endothelial and epithelial layers as well as the stroma which is high in water content. In addition, there are barriers such as tight junctional complexes in the corneal epithelium, lacrimal turnover, nasolacrimal drainage, blinking reflexes, efflux transporters, drug metabolism by ocular enzymes, and drug binding to or repulsion from conjunctival mucins, tear proteins, and melanin. In order to maximize transport through the cornea while minimizing drug loss through other pathways, researchers have developed numerous methods to improve eye drop formulations including the addition of viscosity enhancers, permeability enhancers, mucoadhesives, and vasoconstrictors, or using formulations that include puncta occlusion, nanocarriers, or prodrugs. This review explains the mechanism behind each of these methods, examines their history, analyzes previous and current research, evaluates future applications, and discusses the pros and cons of each technique.

A Review on Polymeric Nano Micelles Based Delivery to the Posterior Segment of the Eye

Introduction: Many nanoformulations have been designed and evaluated for ocular drug delivery system consistently. These nanoformulations are designed for prolonged retention and course time, stable, efficient and reversible drug loading. The ocular bioavailability is very less when the drug is given through topically. Various anatomical and physiological limitations, for example, tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances cause the challenges and delay the ocular drug permeation because of the limitation that less than 5% dose can reach into the ocular tissues. Different types of Polymeric micelles were prepared to overcome the above challenges. Polymeric nano micelles are prepared by different methods, such as direct dissolution, dialysis method, Oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying method.

Nanotechnology for the Treatment of Allergic Conjunctival Diseases.

Allergic conjunctivitis is one of the most common external eye diseases and the prevalence has been increasing. The mainstay of treatment is topical eye drops. However, low bioavailability, low ocular drug penetration, transient resident time on the ocular surface due to tear turnover, frequent topical applications and dependence on patient compliance, are the main drawbacks associated with topical administration. Nanotechnology-based medicine has emerged to circumvent these limitations, by encapsulating the drugs and preventing them from degradation and therefore providing sustained and controlled release. Using a nanotechnology-based approach to load the drug is particularly useful for the delivery of hydrophobic drugs such as immunomodulatory agents, which are commonly used in allergic conjunctival diseases. In this review, different nanotechnology-based drug delivery systems, including nanoemulsions, liposomes, nanomicelles, nanosuspension, polymeric and lipid nanoparticles, and their potential ophthalmic applications, as well as advantages and disadvantages, are discussed. We also summarize the results of present studies on the loading of immunomodulators or nonsteroidal anti-inflammatory drugs to nano-scaled drug delivery systems. For future potential clinical use, research should focus on the optimization of drug delivery designs that provide adequate and effective doses with safe and satisfactory pharmacokinetic and pharmaco-toxic profiles.

Strip meniscometry tube: a rapid method for assessing aqueous deficient dry eye

BackgroundThe aim of this study was to investigate the utility of strip meniscometry tube (SMTube) for the quantitative assessment of the tear film, by comparing it to measurements of tear turnover rate using the gold standard method, fluorophotometry. Also, to determine the viability of this test as a diagnostic tool for aqueous deficient dry eye (ADDE), to inform appropriate clinical management.MethodsThirty‐two participants (15 ADDE; 17 non‐ADDE) were recruited. Tear turnover rate of the right eye of each subject was conducted with an automated scanning fluorophotometer and SMTube test was conducted. Tear meniscus height was assessed using a slitlamp biomicroscope and eyepiece graticule.ResultsSignificant differences between the ADDE and the non‐ADDE groups were found for all measures: tear turnover rate 7.9 ± 1.8 versus 19.6 ± 5.9 per cent/minute (p < 0.001), SMTube 3.2 ± 1.1 versus 5.7 ± 2.3-mm (p = 0.001) and tear meniscus height 0.18 ± 0.05 versus 0.23 ± 0.04-mm (p = 0.004). Moreover, significant correlations were found between tear turnover rate and SMTube (rho = 0.78, p < 0.001), tear turnover rate and tear meniscus height (rho = 0.54, p < 0.001) and SMTube and tear meniscus height (rho = 0.47, p < 0.01). Using a receiver operating characteristic curve, SMTube showed a sensitivity of 67 per cent and a specificity of 88 per cent for the diagnosis of ADDE.ConclusionGiven its performance, availability, speed and the fact it is relatively cheap, the study shows that the SMTube can be used as an alternative to fluorophotometry to assess tear production. It appears from the results that SMTube is a viable minimally invasive test for the diagnosis of ADDE.

Optimization of in-situ Nanoparticulate Gel of Ofloxacin using Factorial Design to Improve Treatment Strategy for Conjunctivitis and Corneal Ulcers

Abstract: Background: One of the main problems in ophthalmic drug delivery is the rapid elimination of conventional liquid eye drops from the eye due to rapid tear turnover resulting precorneal loss because of irritation caused by the drug preparation from large volume of the administered eye drop (~50 μl), a very small amount i.e. <5% of the dosage actually penetrates and is able to reach intraocular tissues. Ofloxacin (OFL), a fluoroquinolone drug is used for the treatment of conjunctivitis and corneal ulcers and it is given quarterly in a day because its bioavailability is very low. The present study was designed to increase the ocular residence time of drug by formulating nanoparticulate in-situ gel for ensuring low irritation, better release and compatibility with ocular tissue. Materials and Methods: Initially, OFL nanoparticles were prepared using single emulsion solvent evaporation method and evaluated for various evaluation parameters. Based on the results, an optimized batch (B3) was selected by applying factorial design; which was further converted into in-situ gel. Results: Results of evaluation parameters revealed that optimized batch (B3) showed significant (p=0.0001 and p=0.0090) increased in particle size and entrapment efficiency in comparison to rest batches. Moreover, nanoparticulate in-situ gel showed satisfactory results. Conclusion: Hence, Ofloxacin nanoparticulate in-situ gel thus formulated showed controlled drug release with lesser dosing frequency. Key words: Ofloxacin, Nanoparticle(s), Nanoparticulate in-situ gel, Conjunctivitis, Factorial design.

Kinetics of Fluorescein in Tear Film After Eye Drop Instillation in Beagle Dogs: Does Size Really Matter?

The study aimed to determine the impact of drop size on tear film pharmacokinetics and assess important physiological parameters associated with ocular drug delivery in dogs. Two separate experiments were conducted in eight healthy Beagle dogs: (i) Instillation of one drop (35 μl) or two drops (70 μl) of 1% fluorescein solution in each eye followed by tear collections with capillary tubes from 0 to 180 min; (ii) Instillation of 10 to 100 μl of 0.1% fluorescein in each eye followed by external photography with blue excitation filter (to capture periocular spillage of fluorescein) and tear collections from 1 to 20 min (to capture tear turnover rate; TTR). Fluorescein concentrations were measured in tear samples with a fluorophotometer. The TTR was estimated based upon non-linear mixed-effects analysis of fluorescein decay curves. Tear film pharmacokinetics were not superior with instillation of two drops vs. one drop based on tear film concentrations, residual tear fluorescence, and area under the fluorescein-time curves (P ≥ 0.163). Reflex TTR varied from 20.2 to 30.5%/min and did not differ significantly (P = 0.935) among volumes instilled (10–100 μl). The volumetric capacity of the canine palpebral fissure (31.3 ± 8.9 μl) was positively correlated with the palpebral fissure length (P = 0.023). Excess solution was spilled over the periocular skin in a volume-dependent manner, predominantly in the lower eyelid, medial canthus and lateral canthus. In sum, a single drop is sufficient for topical administration in dogs. Any excess is lost predominantly by spillage over the periocular skin as well as accelerated nasolacrimal drainage.

Electrospun nanofibers – A promising solid in-situ gelling alternative for ocular drug delivery

A serious problem of the treatment of eye diseases is the very short residence time of the drug. The majority of the drug is cleared within few seconds due to the poor capability of the eye to accommodate additional liquids. We developed a new ocular drug delivery system, which is applied in dry form and forms immediately a gel after administration. The system is based on gellan gum/pullulan electrospun nanofibers. The rheological behavior of the spinning solution was investigated followed by further characterization of the in situ formed gel. Three-dimensional X-ray imaging with nanometric resolution (nano-CT) and electron scanning microscopy were used for a detailed characterization of the diameter and alignment of the fibers. A high porosity (87.5 ± 0.5%) and pore interconnectivity (99%) was found. To ensure a good fit to the eye anatomy, the prepared fibers were shaped into curved geometries. Additionally, a new innovative moistening chamber for the in vitro determination of the ocular residence time in porcine eyes was developed which mimics the tear turnover. A clear prolongation of the fluorescein residence time compared to conventional eye drops was achieved with the application of the curved nanofiber in situ gelling mat. In summary, the developed in situ gelling system with adapted geometry is a promising alternative system for ocular drug delivery.

Fluorophotometric Assessment of Tear Volume and Turnover Rate in Healthy Dogs and Cats.

Purpose: The study establishes normative data of tear volume (TV) and tear turnover rate (TTR) in healthy dogs and cats, 2 species commonly used for translational research in ophthalmology.Methods: Thirty-six dogs and 24 cats were enrolled, encompassing a variety of breeds with diverse skull conformations (brachycephalic, mesocephalic, and dolichocephalic). Two microliters of 10% fluorescein were instilled onto the upper bulbar conjunctiva of both eyes, followed by tear collection with 2-μL capillary tubes at 0, 2, 4, 6, 10, 15, and 20 min. Fluorescein concentrations were measured with a computerized scanning ocular fluorophotometer. The TV and TTR were estimated based upon nonlinear mixed-effects analysis of fluorescein decay curves.Results: In dogs, median (interquartile range) TV, basal TTR (bTTR), and reflex TTR (rTTR) were 65.3 μL (42.3–87.9), 12.2%/min (3.7–22.1), and 50.0%/min (25.9–172.3), respectively. In cats, median (interquartile range) TV, bTTR, and rTTR were 32.1 μL (29.5–39.9), 10.9%/min (3.0–23.7), and 50.0%/min (28.4–89.4), respectively. Body weight (r = 0.44) and age (r = 0.30) were positively correlated (P ≤ 0.019) with TV in dogs. Age was negatively correlated (P ≤ 0.018) with TTR in dogs (r = −0.33) and cats (r = −0.24). However, TV and TTR were not associated with skull conformation in either species.Conclusions: Dogs have greater TV than cats but similar basal and rTTR. Tear parameters were impacted by body weight and age, but not by skull conformation. In both clinical and research settings, successive lacrimal tests should be spaced by ≥10 min to provide sufficient time for the tear film to replenish, as bTTR is ∼11%/min–12%/min in both species.