scholarly journals Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 258
Author(s):  
Elena Peira ◽  
Giulia Chindamo ◽  
Daniela Chirio ◽  
Simona Sapino ◽  
Simonetta Oliaro-Bosso ◽  
...  
Keyword(s):  
Residence Time ◽  
Liquid Crystalline ◽  
Retinal Pigment ◽  
Ion Pairs ◽  
Anterior Segment ◽  
Corneal Opacity ◽  
Eye Drops ◽  
Adhesion Properties ◽  
Oil In Water

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems.

Preclinical Assessment of Nanostructured Liquid Crystalline Particles for the Management of Bacterial Keratitis: in-vivo and Pharmacokinetics Study

2021 ◽  
Author(s):  
Shreya Kaul ◽  
Upendra Nagaich ◽  
Navneet Verma
Keyword(s):  
Residence Time ◽  
Liquid Crystalline ◽  
Ex Vivo ◽  
Research Work ◽  
Poloxamer 407 ◽  
Pharmacokinetic Studies ◽  
Eye Drops ◽  
Statistical Experimental Design ◽  
Bacterial Keratitis

Abstract The research work was driven to develop novel nanostructured liquid crystalline particles of vancomycin for its improved pre-ocular residence time, ocular bio-availability, enhanced targeting, increased permeability, reduced dosing frequency, controlled drug release and reduced systemic side-effects. Formulation was developed by fragmenting cubic crystalline phase of glycerol monooleate, water and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex-vivo transcorneal permeation studies demonstrated that the optimized cubosomes had 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution. Whereas, in-vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered in day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated level of drug in aqueous humor and results revealed that the time to peak concentration (Tmax) of vancomycin loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating safety of formulation. In conclusion, results manifested that the developed vancomycin loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye-drops for the management of bacterial-keratitis.

scholarly journals Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye

2021 ◽  
Vol 22 (22) ◽  
pp. 12368
Author(s):  
Alexander Vaneev ◽  
Victoria Tikhomirova ◽  
Natalia Chesnokova ◽  
Ekaterina Popova ◽  
Olga Beznos ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anterior Segment ◽  
Drug Carriers ◽  
Ocular Tissue ◽  
Eye Drops ◽  
Topical Drug Delivery ◽  
Natural Polymers ◽  
Drug Bioavailability ◽  
Sustained Drug Release

Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients. However, conventional drug formulations are usually characterized by short retention time in the tear film, insufficient contact with epithelium, fast elimination, and difficulties in overcoming ocular tissue barriers. Not more than 5% of the total drug dose administered in eye drops reaches the interior ocular tissues. To overcome the ocular drug delivery barriers and improve drug bioavailability, various conventional and novel drug delivery systems have been developed. Among these, nanosize carriers are the most attractive. The review is focused on the different drug carriers, such as synthetic and natural polymers, as well as inorganic carriers, with special attention to nanoparticles and nanomicelles. Studies in vitro and in vivo have demonstrated that new formulations could help to improve the bioavailability of the drugs, provide sustained drug release, enhance and prolong their therapeutic action. Promising results were obtained with drug-loaded nanoparticles included in in situ gel.

scholarly journals Insight into the Lubrication and Adhesion Properties of Hyaluronan for Ocular Drug Delivery

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1431
Author(s):  
Mikuláš Černohlávek ◽  
Martina Brandejsová ◽  
Petr Štěpán ◽  
Hana Vagnerová ◽  
Martina Hermannová ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Friction Coefficient ◽  
Human Keratinocytes ◽  
Eye Disease ◽  
Low Molecular Weight ◽  
Eye Drops ◽  
Adhesion Properties ◽  
Physiochemical Properties ◽  
Insight Into

Hyaluronan (HA) is widely used for eye drops as lubricant to counteract dry eye disease. High and low molecular weight HA are currently used in ophthalmology. However, a large portion of the current literature on friction and lubrication addresses articular (joint) cartilage. Therefore, eye drops compositions based on HA and its derivatized forms are extensively characterized providing data on the tribological and mucoadhesive properties. The physiochemical properties are investigated in buffers used commonly in eye drops formulations. The tribological investigation reveals that amphiphilic HA-C12 decreases the friction coefficient. At the same time, the combination of trehalose/HA or HAC12 enhances up to eighty-fold the mucoadhesiveness. Thus, it is predicted a prolonged residence time on the surface of the eye. The incorporation of trehalose enhances the protection of human keratinocytes (HaCaT) cells, as demonstrated in an in-vitro cell-desiccation model. The presence of trehalose increases the friction coefficient. Medium molecular weight HA shows significantly lower friction coefficient than high molecular weight HA. This research represents a first, wide array of features of diverse HA forms for eye drops contributing to increase the knowledge of these preparations. The results here presented also provide valuable information for the design of highly performing HA-formulations addressing specific needs before preclinic.

scholarly journals Corneal Opacity Induced by Antiglaucoma Agents Other Than Brimonidine Tartrate

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Yuka Kasuya ◽  
Ichiya Sano ◽  
Shinji Makino ◽  
Hidetoshi Kawashima
Keyword(s):  
Anterior Segment ◽  
Corneal Stroma ◽  
Corneal Opacity ◽  
Eye Drops ◽  
Timolol Maleate ◽  
Normal Range ◽  
Topical Drugs ◽  
Antiglaucoma Agents ◽  
Brimonidine Tartrate

The aim of this study is to report a patient with corneal opacity that developed after the use of topical antiglaucoma medications other than brimonidine tartrate (BT). An 85-year-old woman presented with corneal opacity and neovascularization in both eyes. A diagnosis of glaucoma was made 20 years previously, and antiglaucoma agents were prescribed (latanoprost, tafluprost, timolol maleate, travoprost, bimatoprost, ripasudil hydrochloride hydrate, and brinzolamide/timolol maleate) for both eyes. Ocular examination revealed semicircular fan-shaped corneal sterile infiltration with neovascularization. Anterior-segment optical coherence tomography (OCT) showed marked corneal opacity and thickened corneal stroma. The topical drugs were discontinued and replaced with 0.1% betamethasone eye drops. Two weeks after topical drugs were discontinued and replaced with betamethasone, the corneal sterile infiltration markedly improved, although the corneal opacity remained across the stromal layer. In addition, corneal opacity, intermixed with separate transparent sections, was observed as a striped shape. OCT showed an improvement of the thickened corneal stroma. Six weeks after the initial visit, the remaining corneal opacity could be seen as a mixture of opaque and nonopaque areas in stripes. The corneal stromal thickness decreased almost back to the normal range, while the area of the corneal opacity remained unchanged. In vivo laser confocal microscopy showed hyperreflective materials with needle-like structures in the corneal stroma. The corneal opacity showed several similarities to the previous reports of the cases treated with BT. Therefore, clinicians should be mindful of a possible development of corneal opacity in patients treated with antiglaucoma medications other than BT.

scholarly journals Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1213 ◽  
Author(s):  
Miguel Gómez-Ballesteros ◽  
Vanessa Andrés-Guerrero ◽  
Francisco Parra ◽  
Jorge Marinich ◽  
Beatriz de-las-Heras ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
In Vitro Release ◽  
Anterior Segment ◽  
Drug Carriers ◽  
Eye Drops ◽  
Hypotensive Drug ◽  
Ocular Drugs ◽  
Ophthalmic Drug ◽  
Conventional Solution

Topical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that affect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma. However, large ACZ doses are needed which results in systemic side effects. Recently, we synthesized copolymers based on 2-hydroxyethyl methacrylate (HEMA) and a functionalized three-arm poloxamer star (Bayfit-MA). The new material (HEMA/Bayfit-MA) was engineered to be transformed into nanoparticles without the use of surfactants, which represents a significant step forward in developing new ophthalmic drug delivery platforms. Acetazolamide-loaded nanocarriers (ACZ-NPs) were prepared via dialysis (224 ± 19 nm, −17.2 ± 0.4 mV). The in vitro release rate of ACZ was constant over 24 h (cumulative delivery of ACZ: 83.3 ± 8.4%). Following standard specifications, ACZ-NPs were not cytotoxic in vitro in cornea, conjunctiva, and macrophages. In normotensive rabbits, ACZ-NPs generated a significant intraocular pressure reduction compared to a conventional solution of ACZ (16.4% versus 9.6%) with the same dose of the hypotensive drug (20 µg). In comparison to previously reported studies, this formulation reduced intraocular pressure with a lower dose of ACZ. In summary, HEMA:Bayfit-MA nanoparticles may be a promising system for ocular topical treatments, showing an enhanced ocular bioavailability of ACZ after a single instillation on the ocular surface.

scholarly journals Celastrol-based nanomedicine promotes corneal allograft survival

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhanrong Li ◽  
Ruixing Liu ◽  
Zhihua Guo ◽  
Dandan Chu ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Corneal Transplantation ◽  
Anterior Segment ◽  
Eye Drops ◽  
Allograft Survival ◽  
Corneal Permeability ◽  
Corneal Allograft ◽  
M1 Macrophage

AbstractEffectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases. Graphical Abstract

scholarly journals In Situ Liquid Crystal Gel as a New Ophthalmic Drug Delivery System for Pilocarpine Nitrate: Improving Preocular Retention and Ocular Bioavailability

2021 ◽  
Author(s):  
Wenqing Wu ◽  
Wenxuan Cao ◽  
Ye Cai ◽  
Menghe Zhang ◽  
Tiantian Chen ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Internal Structure ◽  
Residence Time ◽  
Delivery System ◽  
High Efficiency ◽  
Eye Drops ◽  
Eye Irritation ◽  
Irritation Test

Abstract The purpose of this article is to develop an in-situ liquid crystal gel that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). The phytantriol (PT) -based in situ liquid crystal gels were prepared by a vortex method using PT, PEG400, Triglyceride (TAG) and water (in the ratio of 61.15:30:3.85:5, w/w). Firstly, the internal structure of the PN-loaded liquid crystal gel was characterized by polarizing microscope (PLM), small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and rheology. In vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, eye irritation test，preocular residence time evaluation,were studied in vivo and compared with eye drops.Based on various characterization techniques, it is proved that the internal structure of the gel is a hexagonal phase.In vitro release results identified that PN could be released continuously from HII gel over a period of 24 h. The in vitro obvious permeability coefficient of HII gel was 3.19-fold (P < 0.01) higher than that of the eye drops. Compared with eye drops,the HII gel had good bioadhesion and displayed longer residence time on the eyeballs surface using fluorescent labeling technology.In addition, through Corneal hydration level and eye irritation test ., it is conjectured that HII gel will not cause eye irritation. In short, the formulation has the advantages of high efficiency, slow release and non-toxicity, and will become a promising pharmaceutical strategy to improve the efficacy of glaucoma.

Use of light microscopy in the qualitative and quantitative study of liquid crystalline order

1992 ◽  
Vol 50 (1) ◽  
pp. 264-265
Author(s):  
Christopher Viney
Keyword(s):  
Light Microscopy ◽  
Liquid Crystalline ◽  
Structural Characteristics ◽  
Molecular Order ◽  
Liquid Crystalline Phases ◽  
Convenient Technique ◽  
Liquid Crystalline Materials ◽  
Transparent Windows

Light microscopy is a convenient technique for characterizing molecular order in fluid liquid crystalline materials. Microstructures can usually be observed under the actual conditions that promote the formation of liquid crystalline phases, whether or not a solvent is required, and at temperatures that can range from the boiling point of nitrogen to 600°C. It is relatively easy to produce specimens that are sufficiently thin and flat, simply by confining a droplet between glass cover slides. Specimens do not need to be conducting, and they do not have to be maintained in a vacuum. Drybox or other controlled environmental conditions can be maintained in a sealed chamber equipped with transparent windows; some heating/ freezing stages can be used for this purpose. It is relatively easy to construct a modified stage so that the generation and relaxation of global molecular order can be observed while specimens are being sheared, simulating flow conditions that exist during processing. Also, light only rarely affects the chemical composition or molecular weight distribution of the sample. Because little or no processing is required after collecting the sample, one can be confident that biologically derived materials will reveal many of their in vivo structural characteristics, even though microscopy is performed in vitro.

Working conditions and occupational risks of anterior eye pathology in metalworking machine operators

2020 ◽  
pp. 462-467
Author(s):  
N. I. Latyshevskaya ◽  
M. A. Alborova ◽  
L. A. Davydenko ◽  
A. V. Belyaevа
Keyword(s):  
Working Conditions ◽  
Work Experience ◽  
Anterior Segment ◽  
Tear Film ◽  
Corneal Opacity ◽  
Occupational Risks ◽  
Machine Operators ◽  
Comparison Groups ◽  
Working Groups ◽  
Visual Organ

Introduction. The profession of “machine operator in metalworking”, one of the most common professions in various industries, characterized by a large volume of abrasive operations, accompanied by dust formation, which creates a potential for the occurrence of diseases of the visual organ.The aim of the study is to provide a hygienic assessment of working conditions and occupational risk of visual organ pathology in metalworking machine operators.Materials and methods. Observation groups — machine operators for metalworking of two training groups (experience up to 5 years, experience of 6–20 years). Two comparison groups (administrative and technical personnel of the enterprise) are formed according to the same age-experience principle.Results. The working conditions of machine operators were classified as class 3.2. taking into account the severity and intensity of the work process and the noise level (80 dBA) in the workplace. Nitrogen oxide, carbon monoxide, and manganese were registered in the air of the working area in concentrations below the permissible concentration (PC), and the aerosol dihydroxide was registered above the PC in 25.8% of cases. In the main working groups, diseases of the anterior segment of the eye were more often registered, among which dry eye syndrome (DYS) prevailed (94.1%), chronic blepharoconjunctivitis (79.9%), persistent corneal opacification (21.7%). There was an increase in the prevalence of detected diseases with an increase in work experience (p≤0.05). In machine operators, the frequency of inhibition of lacrimal formation and decreased stability of the tear film was recorded significantly more often, with increasing work experience, the degree of violation of lacrimal formation and stability of the tear film increased. The chances of detecting pathology of the anterior segment of the eye in machine operators are 5.9 and 3.5 times higher than in the comparison group. There are different forces of connection, increasing with the increase of work experience in the profession, between the working conditions of machine operators and the occurrence of SHG (relatively strong), with chronic blepharoconjunctivitis and persistent corneal opacity (medium strength), which suggests the professional conditionality of this pathology.Conclusions. The results obtained suggest that the pathology of the anterior segment of the eye is professionally conditioned in metalworking machine operators and necessitate the introduction of preventive measures aimed at protecting the visual organ.

Formulation and Evaluation of Fish Oil-based Rizatriptan Microemulsion for Intranasal Migraine Treatment

2015 ◽  
Vol 8 (3) ◽  
pp. 2972-2978
Author(s):  
Kanchan P Upadhye ◽  
Divya Senpal ◽  
Minakshee Nimbalwar ◽  
Gouri Dixit
Keyword(s):  
Fish Oil ◽  
Nasal Cavity ◽  
Residence Time ◽  
Stability Study ◽  
Migraine Treatment ◽  
Existence Region ◽  
Microemulsion Based Gel ◽  
Micro Emulsion ◽  
Pseudoternary Phase Diagram

In the present study microemulsion based intranasal gel of rizatriptan using fish oil was prepared for treatment and management of migraine to sustain the drug release and improve the drug residence time in nasal cavity. Fish oil is reported to have antimigraine activity hence it has been used in the present formulation along with cremophore EL as surfactant and Transcutol P as co-surfactant. The pseudoternary phase diagram plotted with these components shown the microemulsion existence region in ratio of (1:9-9:1) surfactant and co-surfactant. The optimized micro-emulsion contained fish oil (45.29%), cremophore E/transcutol P (2:1) and was characterized for pH (6.3±0.02), viscosity (114 ± 3.00cp), % transmittance (99.5 ± 1.01), refractive index (1.335±0.01),). The prepared microemulsion gels were optimized and characterized for in-vitro studies, pH, drug content, rheological studies and stability study. The release of rizatriptan from micro-emulsion gel prepared from carbopol 934 (98.01%) was found to be higher and prolonged than plain gel. Thus, microemulsion based gel was able to prolong drug releaseand improve drug residence time in the nasal cavity. 

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