Commercial Eye Drops Research Articles

In vitro validation of the amoebicidal activity of commercial eye drops as second activity

The validation of anti-Acanthamoeba activity of commercial eye drops has gained a great interest recently and a growing number of commercials eye drop were evaluated for their aptitude to inhibit Acanthamoeba as a second pharmacological effect. In the present study, three different eye drops, commercializing in Spain, including TobraDex, Cusimolol and Colircusi antiedema have been tested in vitro against trophozoites and cysts stage of the facultative pathogen Acanthamoeba. The alamarBlue™ method was used to evaluate both trophocidal and cysticidal properties. The most active eye drops were tested for their impact on some programmed cell death features. We found out that the cells inhibition was strain and eye drop dependent, and 5% eye drop was able to eliminate both trophozoite and cyst stage of Acanthamoeba spp. A treatment of 24 h with 5% of TobraDex or Cusimolol was able to show DNA condensation, collapse in the mitochondrial membrane potential and reduction of the ATP level production in Acanthamoeba. We could assume that the present eye drops could induce programed cell death like process in Acanthamoeba via mitochondrial pathway.

Imprinted β-ketoenamine-linked covalent organic frameworks as dispersive sorbents for the fluorometric determination of timolol.

Timolol accompanied the formation of fluorescent β-ketoenamine-linked covalent organic frameworks (COFs) via the Sc(Tof)3-catalyzed condensation of derivated carbaldehyde and hydrazide in a 1,4-dioxane/mesitylene porogen to construct timolol-imprinted COFs (TICOFs). With high imprinting factors, the synthesis-optimized TICOFs were characterized by fluorescence, UV-Vis spectrometry, X-ray diffraction, N2 adsorption/desorption analyses, scanning electron microscopy, and FTIR spectrometry. The TICOF fluorescence measured at 390nm/510nm isdynamically quenched by timolol and was thus utilized to quantify timolol in a linear range of 25-500nM with a LOD of 8nM. The TICOF recovered 99.4% of 0.5% timolol maleate in a commercial eye drop (RSD = 1.1%, n = 5). In addition, TICOF was used as a dispersive sorbent to recover 95% of 2.0nM timolol from 20mg of TICOF in 25mL phosphate buffer. Dilution factors of 25 and 75 were the maximum tolerated proportions of the urine and serum matrix spiked with 2.0nM timolol to reach recoveries of 92.4% and 90.3%, respectively.

Besifloxacin-loaded ocular nanoemulsions: design, formulation and efficacy evaluation.

The purpose of this study was to develop and evaluate nanoemulsions (NEs) containing besifloxacin for ocular drug delivery. Pseudo ternary phase diagrams were constructed using Triacetin (oil), Cremophor® RH 40 (surfactant), and Transcutol®P (co-surfactant) to identify NE regions. Six formulations were developed by low-energy emulsification method and then evaluated for size, refractive index, pH, osmolality, viscosity, anddrug release.After accelerated physical stability and bovine conrneal permeation studies,NE2 was chosen as optimized formulationforantimicrobial efficacy, and hen's egg test-chorioallantoic membrane (HET-CAM)tests. The particle size of optimum NE was 14nm with a narrow size distribution. Moreover, other physicochemical characterizations were in the acceptable range for ocular administration. Besifloxacin-loaded NEs demonstrated sustained release pattern and 1.7-fold higher permeation compared with the control suspension in the ex vivo transcorneal permeation study. HET-CAM test indicated no irritation, and HL% revealed no damage to the tissue, so the optimum NE is well tolerated by the eye. In vitro antimicrobial evaluation, showed comparative efficacy of lower drug-loaded NE (0.2%) versus 0.6% besifloxacin suspension (equal concentration to commercial besifloxacin eye drop). In conclusion, besifloxacin-loaded NEs could be considered as a suitable alternative to the marketed suspension for treatingbacterial eyeinfections.

Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells.

BackgroundExtracellular vesicles (EVs) are capable of manipulating cellular functions for the maintenance of biological homeostasis and disease progression, such as in glaucoma disease. These nano-particles carry a net negative surface charge under physiological conditions that can contribute to EVs:EVs interaction and their uptake by target cells.PurposeTo investigate the effect of glaucoma drugs on EVs physicochemical characters and the implications for their uptake by trabecular meshwork (TM) cells.MethodsTM or non-pigmented ciliary epithelium (NPCE) cells derived EVs were incubated with commercial anti-glaucoma formulation, Timolol maleate, Brinzolamide or Benzalkonium Cl and their size and zeta potential (ZP) and physical interactions of EVs derived from NPCE cells and TM cells were evaluated. The contribution of EVs interactions to up-take by TM cells was examined using fluorescence-activated cell sorting.ResultsEVs size and ZP were affected by the ionic strength of the buffer rather than EVs type. Commercial glaucoma eye drops, including β-blocker, α-2-agonist and prostaglandin analogs, reduced NPCE EVs ZP, whereas exposure of EVs to carbonic anhydrase inhibitor caused an increase in the ZP. A correlation was found between increased ZP values and increased NPCE EVs uptake by TM cells. We were able to show that Benzalkonium chloride stands behind this ZP effect and not Timolol or Brinzolamide.ConclusionAltogether, our findings demonstrate that EVs size, surface membrane charge, and ionic strength of the surrounding have an impact on EVs:EVs interactions, which affect the uptake of NPCE EVs by TM cells.

Use of the corneal bioreactor to assess deswelling efficacy of hyperosmotic eye drops

AbstractPurposeThe preclinical testing of the efficacy and safety of hyperosmotic anti‐edematous eye drops is complicated by the lack of a simple in vivo and ex vivo animal model. Our patented corneal bioreactor (BR) allows prolonged preservation of the human cornea by restoring physiological intraocular pressure and renewing the culture medium. Under certain experimental conditions, the corneas preserved in BR are nevertheless thicker than normal (684 ± 52 um, A J Transplantation 2019).AimTo use this characteristic of corneas stored in the BR to test the efficacy of new hyperosmotic eye drops prototypes.MethodsHuman corneas (n = 4) discarded by our eye banks were used whatever their endothelial status. They were first stored for 2 weeks into the BR filled with CorneaMax (Eurobio, France), with 21 mmHg in the endothelial chamber to allow regeneration of a normal epithelium as previously shown. Using a specific BR lid allowing sterile instillation in front of corneal center, each cornea was treated topically with 3 drops, every 2 hr, repeated 3 times. The epithelial chamber was emptied just before instillation and filled again with CorneaMax 2 min after instillation. Three corneas were treated with a commercial eyedrop containing 5% NaCl and 0.15% sodium hyaluronate and one cornea with Balanced Salt Solution (BSS) as a control. Central corneal volume (on an 8mm disc, CCV8 in mm3) was measured with OCT (Casia, Tomey) immediately before and after each instillation. The decrease in CCV was calculated for each instillation and before the first and the third instillation.ResultsFor corneas treated with NACl 5%, CCV decreased by (mean ± SD) 1.0 ± 0.4, 0.7 ± 0.1 and 0.6 ± 0.2 mm3, respectively, for the first, the second and the third instillation, and globally by 2.4 ± 1.1 mm3. The cornea treated with BSS remained unchanged.ConclusionsThe BR is an efficient tool to quantify the efficacy of hyperosmotic eye drops designed to deswell human cornea.

Improved Ocular Bioavailability of Moxifloxacin HCl using PLGA Nanoparticles: Fabrication, Characterization, In-vitro and In-vivo Evaluation.

Improving the bioavailability of a drug at the ocular surface presents a profound challenge. Due to ocular physiological barriers, conventional eye drops exhibit poor bioavailability of drugs. Sustained-release nanoparticles may improve the residence time and hence increase absorption of the drug from the corneal surface. The current study focuses on the development of a nanoparticle-based system for the ophthalmic sustained delivery of moxifloxacin, to enhance ocular retention and bioavailability of the drug. PLGA was used as the matrix-forming polymer in the nanoparticle formulation. Nanoparticles were manufactured using a double emulsion (w/o/w) solvent evaporation technique. The formulation was optimized based on physicochemical properties, including size, polydispersity index, and stability. Nanoparticles were also evaluated for in-vitro drug release and pharmacokinetic evaluation in a rabbit model. The optimized formulation exhibited a relatively high initial release rate for six hours followed by sustained release of a drug via diffusion. The in-vivo ocular tolerance studies confirmed that moxifloxacin-loaded PLGA nanoparticles were non-irritating to the eye. The pharmacokinetic studies revealed that the nanoparticles provided a high Cmax, AUC, MRT, and low clearance rate when compared to commercial eye drops. It can be concluded that such PLGA nanoparticles offer the potential for improved bioavailability of moxifloxacin HCl.

Gelling hypotonic polymer solution for extended topical drug delivery to the eye.

Eye-drop formulations should hold as high a concentration of soluble drug in contact with ocular epithelium for as long as possible. However, eye tears and frequent blinking limit drug retention on the ocular surface, and gelling drops typically form clumps that blur vision. Here, we describe a gelling hypotonic solution containing a low concentration of a thermosensitive triblock copolymer, for extended ocular drug delivery. On topical application, the hypotonic formulation forms a highly uniform and clear thin layer that conforms to the ocular surface and resists clearance from blinking, significantly increasing the intraocular absorption of hydrophilic and hydrophobic drugs and extending the drug–ocular-epithelium contact time with respect to conventional thermosensitive gelling formulations and commercial eye drops. We also show that the conformal gel layer allows for therapeutically relevant drug delivery to the eyeball’s posterior segment in pigs. Our findings highlight the importance of formulations that conform to the ocular surface prior to viscosity enhancement, for increased and prolonged ocular-surface contact and drug absorption.

Alternative mydriasis techniques for retinopathy of prematurity screening.

There is a large variation in mydriatic regimens used in screening for retinopathy in preterm infants. Except for the standard instillation of mydriatic drops in their commercial formulation, other techniques for pupil dilation have also been described. This study aimed to review all techniques that have been used for mydriasis in retinopathy of prematurity eye examination (ROPEE) screening. A comprehensive literature search was performed in PubMed, Cochrane library, Trip database, and Scopus, using the key words: "mydriasis", "techniques", "mydriatics", "dilating drops", "retinopathy of prematurity", "ROP", "phenylephrine", "cyclopentolate", "tropicamide", "smaller mydriatic drops", "reduction in drop size" to February 2019. Five primary studies were included, assessing the techniques of microdrops, lower conjunctival fornix (LCF) packing and Mydriasert® ophthalmic insert. Reported efficacy was similar to commercial eyedrops instillation. Microdrops appeared to have a superior safety profile. LCF packing and Mydriasert lead to increased blood pressure, without serious complications, necessitating further safety studies. Of all alternative mydriasis techniques for ROPEE screening that have been described, microdrops appear to be the safest yet still effective technique in the fragile population of premature infants in risk of ROP.

Eudragit RL100 Based Moxifloxacin Hydrochloride and Ketorolac Tromethamine Combination Nanoparticulate System for Ocular Drug Delivery.

Bacterial conjunctivitis is a serious ocular infection if left untreated. It is caused by several species of bacteria like Pseudomonas, Staphylococcus and Mycobacterium. The present investigation explores the development and characterization of moxifloxacin hydrochloride and ketorolac tromethamine combination loaded Eudragit RL 100 nanosuspension for ocular drug delivery in order to overcome the problems associated with conventional dosage forms. The nanosuspension prepared by nanoprecipitation technique showed successful entrapment of both water-soluble drugs in the polymer matrix indicated by their % entrapment efficiencies. Formulations showed a mean particle size <200 nm with narrow size distribution and positive surface charge due to the presence of quaternary ammonium groups of Eudragit RL100. FTIR study revealed compatibility among the components, while a reduction in the crystallinity of formulation was observed in the PXRD study. The release of both the drugs was found to be sustained in nanosuspension as compared to commercial eyedrops. Ex vivo studies showed increased transcorneal permeation of drugs from nanosuspension, where approximately 2.5-fold and 2-fold increase in the permeation was observed for moxifloxacin hydrochloride and ketorolac tromethamine, respectively. The formulation was stable at 4°C and room temperature. Due to their sustained release, positive surface charge and higher transcorneal permeation, this will be a promising ocular drug delivery.

Combined Amoebicidal Effect of Atorvastatin and Commercial Eye Drops against Acanthamoeba castellanii Neff: In Vitro Assay Based on Mixture Design.

The establishment of an effective therapeutic agent against Acanthamoeba keratitis (AK), remains until present, an issue to be solved due to the existence of a cyst stage in the life cycle of Acanthamoeba. Moreover, the effectiveness of the current standard therapeutic agents varies depending on the tested Acanthamoeba strains and its resistance pattern. In the present study, two 10-point augmented simplex-centroid designs were used to formulate a three-component mixture system using water, atorvastatin, and Diclofenaco-lepori or Optiben. The amoebicidal effects and in vitro-induced toxicity in a eukaryotic cell line were determined for all experiments. The optimal mixture to inhibit the parasite without inducing toxicity was established in the first plan as 30% Optiben, 63.5% atorvastatin, and 3.1% water. As for the second experimental design, the optimal mixture to inhibit Acanthamoeba with lower toxicity effect was composed of 17.6% Diclofenaco-lepori and 82.4% atorvastatin.

Comparison of thermosensitive in situ gels and drug-resin complex for ocular drug delivery: In vitro drug release and in vivo tissue distribution.

Conventional ophthalmic eye drops are limited by their rapid elimination rate and short time of action. Ion exchange resin has been used to achieve sustained ocular drug delivery but the high selectivity of drug molecules restricts its broad application. In situ gel system seems to be a good strategy to address these problems but the influence of in situ gel type on the sustained release behavior and tissue distribution after ocular application is unclear. Therefore, in this study, using betaxolol hydrochloride as a model drug, poloxamer 407 and methylcellulose as the carriers, two thermosensitive in situ gel systems were prepared and characterized. Influence of formulation composition type and concentration on in vitro drug release was studied. Tissue distribution after ocular delivery of two different thermosensitive in situ gels was studied and compared with commercial BH eye drop (Betoptic S®). In vitro studies demonstrated that addition of 4% HPMC 606W in 15% P407 solution and 5% PEG4000 in 2% MC solution obtained gels with appropriate gelation temperature and similar sustained drug release rate. In vivo tissue distribution study indicated that they presented similar drug concentration in cornea, iris-ciliary and aqueous humor irrespective of gel type, with higher drug concentration achieved after 4h compared to the commercial resin suspension eye drops. The AUC and MRT of the two in situ gel eye drops were 2 times higher than that of the commercial resin suspension eye drops in cornea. In conclusion, the two thermosensitive in situ gels have prolonged drug release after ocular drug delivery compared with ion exchange resin eye drops, implying their potential applications in clinic with broad drug adoptability.

Anti-microbial Effect and in Vivo Ocular Delivery of Ciprofloxacin-loaded Liposome through Rabbit’s Eye

ABSTRACT Purpose: The main purpose of this study was to increase the concentration and bioavailability of Ciprofloxacin (CPX) in the rabbit eye by liposomal formulation. Methods: CPX- loaded liposomes with and without Carbomer 934 (carbomer) were prepared by a thin-layer hydration method. Liposomal formulations after evaluation for characters such as particle size and entrapment efficiency were used in in-vivo experimental for installation into the rabbit’s eyes. This experimental study consisted of 10 rabbits divided into two groups. Group 1 (liposomes without coating) and group 2 (carbomer coated liposomes) received one drop per h of liposomes consists of 0.3% CPX in the right eye and commercial CPX eye drop in the left eye until 6 h. Aqueous humor and vitreous samples were collected from all rabbits at the baseline, 1, 3 and 6 h and the drug concentration determined by high pressure liquid chromatography (HPLC). On the other hand, minimum inhibitor concentration (MIC) and minimum bactericidal concentration (MBC) of CPX-loaded in liposomes were determined. Results: liposomal formulations increased ocular bioavailability of CPX around four-folds compared with a commercial CPX eye drop. The increase in the ocular bioavailability may be effective and help to treat bacterial endophthalmitis as well as can be used in prophylaxis of post-operative endophthalmitis. Conclusion: The concentrations of CPX on the aqueous humor and vitreous after liposomes application were more than MIC of CPX against pseudomonas auroginosa and staphylococcus aurous but for commercial eye drop was less than MIC. Therefore liposomes modified the pharmacokinetics of CPX and improved pharmacodynamics property.

Reaction-diffusion model as framework for understanding the role of riboflavin in "eye defence" formulations.

Analysis of UV-visible spectra, performed on commercial riboflavin-based eye drops, showed that absorbance is a saturating function of vitamin concentration. This implies a threshold concentration, Ct, such that for riboflavin concentration > Ct the absorbance remains constant and the effectiveness of the eye drops is independent of the dose used. These experimental results were combined with a diffusion–reaction model to elucidate the mechanism of action within the cornea. The model predicts that the eye drops have a low effectiveness on UVB and UVC, while they have a good performance for UVA. Indeed, at the center of the cornea the transmittance is significantly reduced and after 1 h it is reduced by about 70% compared to a cornea devoid of eye drops.

Formulation and Characterization of pH Induced in situ Gels Containing Sulfacetamide Sodium for Ocular Drug Delivery: A Combination of Carbopol®/ HPMC Polymer

Abstract: Introduction: Topical delivery of eye drops which currently accounts to 90% of available ocular dosage forms are ideal for the treatment of eye diseases but having limitations of poor therapeutic response and low bioavailability. Objectives: The objectives of present research was to develop and characterize sustained release in situ ocular gels containing sufacetamide sodium using pH induced gelling polymers for improved therapeutic response and patient compliance. Methods: In situ gel formulations prepared by dispersion method using Carbopol® 940/Carbopol® 934 alone or in combination with hydroxypropyl methylcellulose (HPMC E4M). Formultaions were evaluated for appearance, pH, viscosity, gelling capacity, drug content and in vitro drug release. The optimized formulation was assessed for sterility and antimicrobial efficacy using disk diffusion technique in comparison to commercial eye drops (Albucid®10%). Results: The appearance of in situ gels were clear and free flowing in nature however, a viscous clear solution with no flow was produced for formulations consisting of 0.8% w/v Carbopol® 940/Carbopol® 934 and 2% w/v HPMC E4M. pH of all the formulations was within the range of 5.9 to 6.7. In situ gels with Carbopol® 940 demonstrated higher viscosity compared to Carbopol® 934 and drug release was sustained over a period of 8 h. The selected formulation containing 0.8% w/v Carbopol® 940 and 1.5% w/v HPMC E4M passed sterility test and demonstrated similar antimicrobial efficiency compared to commercial product. Conclusion: Carbopol®/HPMC-based in situ gels have potential to improve patient’s compliance by reducing the dosing frequency and could be a viable alternative to commercial product. Key words: In situ gel, Ocular, Sulfacetamide sodium, Carbopol®/HPMC, in-vitro release, Antimicrobial efficacy.

Nanoemulsion Based Vehicle for Effective Ocular Delivery of Moxifloxacin Using Experimental Design and Pharmacokinetic Study in Rabbits.

Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor® P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1–MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1–MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm2/h) and control (~31.53 µg/cm2/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (Cmax; 555.73 ± 133.34 ng/mL) and delayed Tmax value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (AUC0–8 h) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy.

Dynamic optical coherence tomography imaging of the lacrimal passage with an extrinsic contrast agent.

Recently, in vivo trans-conjunctiva optical coherence tomography (OCT) imaging of the lacrimal passage was demonstrated using a turbid commercial eye drop as an extrinsic contrast agent. However, static OCT images are not sufficient to unambiguously delineate the lumen boundary to render 3D lumen images of the lacrimal passage by segmentation. The turbid eye drop is expected to include small particles that flow and undergo Brownian motion and can be used as an extrinsic contrast agent for dynamic OCT. We conducted dynamic OCT measurements of the lacrimal passage using a swept source OCT system. Firstly, characterization of the dynamic OCT properties of the eye drop was performed. For improved delineation of the lumen boundary, we calculated the sum of the squared differences of intensities with two different normalization parameters. By making composite color images from OCT images and these two dynamic OCT images, we could execute unambiguous segmentation of the lumen of the lacrimal passage. Three-dimensional volumetric images of parts of the lacrimal passage, i.e., lacrimal canaliculus and lacrimal punctum, are demonstrated.

FORMULATION AND EVALUATION OF TROPICAMIDE IN-SITU GELS LOADED SOLID LIPID NANOPARTICLES FOR OCULAR DRUG DELIVERY

The aim of present work Formulation and Evaluation of Tropicamide In-situ Gels loaded Solid Lipid Nanoparticles for Ocular Drug Delivery. The surface morphological of SLN was carried out by TEM. The Tropicamide loaded solid lipid nanoparticles was measured the average particle size was ranges from 182.1+3.12nm to 390.1±2.10 nm. The zeta potential ranges from -0.17±1.4 mV to -3.80±1.5 mV. The entrapment efficiency 66.2 % to 89.2 %. Drug content was ranges from 0.112mg/ml to 0.502 mg/ml. The percentage yield ranges from was ranges from 0.112mg/ml to 0.502 mg/ml. The polydispersity index ranged from 1.011±0.15 to 1.327±0.13. These SLN enriched in Chitosan gels the pH of the formulations range from 6.8 to 6.9. The gelling strength ranged from 129 sec to 152 sec. The bioadhesive force was ranges from 10.21 ±1.15 dynes/cm2 to 15.23 ± 1.22 dynes/cm2. The viscosity was ranges from 2212 ± 1.14 cps to 2420± 1.19 cps. The spreadability coefficient was ranges from 11.2 ± 1.10 gms/sec to 13.3 ± 1.21 gms/sec. The in-vitro diffusion release studies carried out at 12 hrs TSLNGF19 shows the 79.2 ± 0.32. The ex vivo permeation studies for optimized formulation the increased drug permeation and corneal accumulation. In vitro corneal permeation profile of tropicamide loaded SLN from the chitosan gels and commercial eye drop solution (Tropicacyl) across the isolated porcine cornea. The ocular tolerance studies performed with HETCAM assay, corneal hydration study, histopathological studies. The stability studies of chitosan gels for long-term stability as per ICH guidelines (25°C ± 2°C / 60% RH ± 5% RH) &accelerated stability as per ICH guidelines (40°C ± 2°C / 75% RH ± 5% RH) there is no changes in gelling strength, bioadhesive force, viscosity, spreadability coefficient in optimized formulation. Keywords: Chitosan, Corneal hydration studies, ex vivo permeation, in vitro diffusion studies, Solid Lipid Nanoparticles

Nanostructured lipid carriers for intraocular brimonidine localisation: development, in-vitro and in-vivo evaluation

Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97 ± 1.98 nm, negative zeta potential (ZP) of −44.2 ± 7.81 mV, % entrapment efficiency (EE) of 83.631 ± 0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4 °C for 3 months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (−13.14 ± 1.28 mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.

A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model

Ethnopharmacological relevanceIn contrast to other leguminous plants generally used as food, Rhynchosia volubilis Loureiro, a small soybean with a black seed coat, has been used as a traditional oriental remedy for various human diseases in Eastern Asia. In this study, we demonstrated the protective effect of R. volubilis against dry eye disease. Aim of the studyWe aimed to investigate whether a standardized ethanol extract of R. volubilis (EERV) can protect the cornea in a benzalkonium chloride (BAC)-induced mouse dry eye model. Materials and methodsExperimental dry eye was induced by the instillation of 0.2% BAC on mouse cornea. A standardized ethanol extract of R. volubilis (EERV) was orally administered following BAC treatment. The positive control group was treated with commercial eye drops. Fluorescein staining, tear break-up time (BUT), and hematoxylin and eosin staining were evaluated on the ocular surface. Squamous metaplasia and apoptosis in the corneal epithelial layer were detected by immunostaining. Furthermore, the protein expression of cytochrome c, Bcl-2, and Bax was determined. ResultsEERV treatment significantly improved fluorescein scoring, BUT, and smoothness in the cornea compared to the vehicle group. In addition, EERV inhibited squamous metaplasia and apoptosis in the cornea. The expression of cytochrome c and Bax was upregulated, while that of Bcl-2 was downregulated in the vehicle group compared with that in the control group. However, EERV treatment inhibited the expression of cytochrome c and Bax, while that of Bcl-2 was improved. ConclusionStandardized EERV could be a beneficial candidate for the treatment of dry eye disease.

The application of artificial neural networks and support vector regression for simultaneous spectrophotometric determination of commercial eye drop contents

In the present study, artificial neural networks (ANNs) and support vector regression (SVR) as intelligent methods coupled with UV spectroscopy for simultaneous quantitative determination of Dorzolamide (DOR) and Timolol (TIM) in eye drop. Several synthetic mixtures were analyzed for validating the proposed methods. At first, neural network time series, which one type of network from the artificial neural network was employed and its efficiency was evaluated. Afterwards, the radial basis network was applied as another neural network. Results showed that the performance of this method is suitable for predicting. Finally, support vector regression was proposed to construct the Zilomole prediction model. Also, root mean square error (RMSE) and mean recovery (%) were calculated for SVR method. Moreover, the proposed methods were compared to the high-performance liquid chromatography (HPLC) as a reference method. One way analysis of variance (ANOVA) test at the 95% confidence level applied to the comparison results of suggested and reference methods that there were no significant differences between them. Also, the effect of interferences was investigated in spike solutions.