Ophthalmic Drug Delivery System Research Articles

In vitro screening of potential echinochrome delivery systems for the treatment of eye diseases

An important task of topical application of medicines in the treatment of eyes is to achieve a compromise between their effectiveness and safety. The development of new multifunctional local ophthalmic drug delivery systems and in vitro screening of potential medicinal eye products are key areas in solving this problem. In this study, primary in vitro screening of the effect of echinochrome (Ech), the carrageenan complex of echinochrome (CRG/Ech) and its liposomal form (CRG/Ech-Lip) was performed on cultured epithelial cells of the outer shell of the eyeball: conjunctival epithelial cells (Chang Conjunctiva, Clone 1-5c-4) and corneal epithelium human (HCE). The cell viability was assessed by their morphology and metabolic activity using light microscopy and MTT test methods. The direct dependence of the intensity of the cytotoxic effect of Ech on its concentration in the nutrient medium, the form of use, the cellular test system and the incubation time of cells was revealed. Ech in the form of an alcoholic solution in its final concentration of 0.1 mg/ml of the nutrient medium exhibits pronounced cytoxicity against both cellular test systems. The same final concentration of Ech in the nutrient medium, but already as part of the carrageenan complex of echinochrome (CRG/Ech), turned out to be critical only for the viability of corneal epithelial cells, the survival rate of conjunctival cells under these conditions was about 50 %. A high biocompatibility of the liposomal form of the carrageenan complex of echinochrome (CRG/Ech-Lip) with cells of both test systems and a stimulating cytoprotective effect against the cells of the conjunctiva epithelium was revealed.

Review of Development of Ganciclovir as Potential Ophthalmic Drug Delivery Systems

Ganciclovir (GCV) plays a vital role in the treatment and management of ocular viral infections such as Herpes simplex virus (HSV) and cytomegalovirus (CMV) retinitis. However, GCV has low corneal penetration, is poorly permeable across the membrane, and has poor drug bioavailability, which poses a challenge in treating eye diseases. Besides that, conventional topical eye formulations, such as eye drops, gels, and ointments, have limitations such as poor tear turnover, poor residence time of the drug, frequent dosing intervals, wastage of dosage, and excessive systemic absorption leading to poor ocular bioavailability. Many strategies have been investigated to improve corneal permeation and ocular bioavailability of GCV. The journal review was written using the library study method from 2001-2023, which contained information about the Ganciclovir Formulation for Ophthalmic Drug Delivery System. The journal review discussed some approaches to achieving therapeutic goals for GCV. The results of this review showed that some of these approaches, including liposome, microemulsion, nanoparticle microsphere, polymeric nanoparticles, and gold nanoparticles, can improve the limitation of conventional formulation of GCV by increasing penetration, permeability, as well as bioavailability GCV in the ocular.

Self-assembled latanoprost loaded soluplus nanomicelles as an ophthalmic drug delivery system for the management of glaucoma

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability.

Development of FK506-loaded maleimide-functionalized cationic niosomes for prolonged retention and therapeutic efficacy in dry eye disease.

Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy. FK506 M-CNS had a particle size of 87.69 ± 1.05nm and zeta potential of 22.06 ± 1.01 mV. Results of histological evaluation through H&E staining and in vitro cytotoxicity of human corneal epithelial cells consistently revealed the excellent biocompatibility of FK506 M-CNS. FK506 M-CNS exhibited superior ocular retention compared to the market product Talymus®. FK506 M-CNS significantly alleviated the symptoms of DED and promoted the recovery of corneal epithelia. FK506 M-CNS group had the lowest expression levels of inflammatory factors associated with DED. These superiorities might be due to the electrostatic interaction between cationic niosomes and negatively charged mucin in the eye, and the covalent binding of maleimide with the thiol group in the mucin. The maleimide group improved the ocular retention and efficacy of FK506, but did not increase the toxicity. Results indicated that FK506 M-CNS had great potential as a nanopharmaceutical in the treatment of ocular diseases, and M-CNS could be a promising drug carrier for ophthalmic drug delivery systems.

Applications of Nanotechnology-mediated Herbal Nanosystems for Ophthalmic Drug.

In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved biopharmaceutical properties.

A review on topical ophthalmic drug delivery system: Reference to viscosity enhancer.

The eye is the most accessible site for topical drug delivery. Drug's ocular bioavailability is quite low when administered topically as eye drops. Viscosity enhancers are used to increase ocular bioavailability by extending the precorneal residence time of the drug at the ocular site. Cellulose, polyalcohol and polyacrylic acid are examples of hydrophilic viscosity enhancers. The addition of viscosity modifiers increases the amount of time the drug is in contact with the ocular surface. Several polysaccharides have been studied as excipients and viscosity boosters for ocular formulations, including cellulose derivatives such as chitosan (CS), xyloglucan and arabinogalactan (methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose). Viscosity-increasing substances reduce the surface tension, extend the corneal contact time, slow the drainage, and improve the bioavailability. Chitosan is a viscosity enhancer that was originally thought to open tight junction barrier cells in the epithelium. Chitosan thickens the medication solution and allows it to penetrate deeper. Alginate is an anionic polymer with carboxyl end groups that has the highest mucoadhesive strength and is used to improve penetration. Carboxymethylcellulose (CMC), a polysaccharide with a high molecular weight, is one of the most common viscous polymers used in artificial tears to achieve their longer ocular surface residence period. Hyaluronic acid (HA) is biocompatible and biodegradable in nature, and it is available in ocular sustained-release dose forms. A polymer known as xanthan gum is used to increase viscosity. At 0.2% concentration, carbomer forms a highly viscous gel.

A Review on Ophthalmic Drug Delivery System

A Review on Ophthalmic Drug Delivery System

A Survey on Ocular in Situ Gel: An Original Medication Conveyance Framework

In medication delivery system for the eyes the difficult part is to administer drug to the complex anatomical structure of eye. The residence time and bioavailability are the two major problems in conventional ophthalmic drug delivery system while designing a dosage form (eye drops, eye lotions, eye ointments) in order to address eye conditions. To combat these problems a novel drug a technique for delivering drugs termed In Situ Gel eye medication has been developed. Delivery system which is safe easy and effective. Furthermore bioavailability, precorneal residence duration can be increased and frequency of administration, side effect, drug loss owing to tearing can be decreased. In-situ gel production system are methods of delivering drugs that, before being administered to the body, are in solution form but require in situ gelation to change into a gel when activated by environmental stimuli including temperature, pH, and other factors.

A review on nanotechnology based ophthalmic drug delivery system

The field of ophthalmic drug delivery has witnessed significant advancements through the integration of nanotechnology. Despite having numerous conventional dosage forms employed in the ocular drug delivery system the problem of less bioavailability and less retention time is a significant concern. Along with it there are various barriers also involved that affects the drug permeability, solubility due to the lower residence time of the drug on ocular surface. To overcome these problems the nanotechnology approach can be most suitable. All nanocarriers have emerged as a promising career for precise drug targeting to ocular tissues. Their small size, biocompatibility and surface modification enable improved drug solubility, sustained release and enhanced bioavailability. Moreover nanotechnology facilitates the incorporation of therapeutic agents for various ocular conditions, including glaucoma, macular degeneration and infections. These advancements aim to overcome the challenges and barriers in ocular drug delivery system. This review underscores the immense potential of nanotechnology to revolutionize ophthalmic drug delivery, offering the prospect of more efficient and patient-friendly treatments for ophthalmic disorders.
 Keywords: Ocular drug delivery, Nanotechnology, Nanocarriers, Intraocular pressure, Ophthalmic barriers

New ophthalmic drug delivery systems

For decades, topical ophthalmic drug administration through the use of eye drops has been the most widely used technique for the treatment of eye diseases. The development of galenic formulation has led to the use and commercialization of new formulations, such as suspensions, emulsions, and ophthalmic ointments that increase residence time in the site of action. Recently, new administration systems have been developed, such as devices and inserts that provide the sustained release of active substance. Some of these systems are already available on the market, whereas others are still undergoing clinical trials, such as promising systems based on nanostructures (nanocapsules, cyclodextrins, nanoemulsions, etc.). Similarly, various formulations and devices have been developed in the field of intravitreal administration, with different implants available on the European market for the treatment of age-related macular degeneration (AMD), diabetic macular edema, or infections that affect the posterior segment. This review includes current developments in ophthalmic topical and intravitreal drug administration routes as well as those under investigation.

DEVELOPMENT AND CHARACTERIZATION OF FLURBIPROFEN LOADED NIOSOMAL IN-SITU GEL FOR OPHTHALMIC DRUG DELIVERY SYSTEM

Niosome are non-ionic surfactant-based liposomes, obtained in the hydration of artificial non-ionic surfactants, without or with addition of cholesterol or additional lipids. The intention of the current study was to organize and evaluate the in-situ niosomal gel loaded with flurbeprofen for the ophthalmic drug delivery system. Flurbeprofen, a nonsteroidal anti- infammatory drug (NSAIDs) is used to relief pain and inflammation. It carries out anti- inflammatory, analgesic and antipyretic activities. Flurbeprofen loaded Niosomes investigate the connection among the non-ionic drug / surfactant ratio with the adding of cholesterol was successfully organized with the thin film hydration way and compare the result of different grade of span used (20, 40 and 60) with the different ratio of cholesterol. Niosomes have been identified by drug entrapment efficiency, drug content, particle size and in-vitro diffusion study. Niosomes prepared using span 60 and cholesterol in the ratio (1:1) f4 showed greater entrapment efficiency (79.2%).

Perspective use of bio-adhesive liquid crystals as ophthalmic drug delivery systems

The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.

Daily disposable contact lenses as a platform for ocular drug delivery of cyclosporine A

Ophthalmic drug delivery is an important area of research that aims to improve the efficacy and convenience of treatment for various eye conditions. There are multiple ways in which drugs can be delivered to the eye, including eye drops, ointments, gels, and inserts. The most prevalent way of administering medication to the eye is through eye drops. They are easy to use and can be self-administered by patients. Nonetheless, eye drops have the disadvantage of being prone to removal by tears, which may result in insufficient drug absorption and reduced effectiveness. Irregular use of active substances can exacerbate the disease, resulting in prolonged treatment with questionable efficacy. Soft contact lenses that serve as ophthalmic drug delivery systems (DDS) can become a viable substitute for traditional treatments. These polymeric lenses can be embedded with various active compounds, some of which are not readily soluble in water or physiological fluids. One such drug is Cyclosporine A (CyA), an immunosuppressant with a high molecular weight and hydrophobic properties, chronically used to treat dry eye syndrome (DES). The article discusses the development of a method for modifying Hilafilcon B contact lenses obtained from drugstores with Cyclosporine A (CyA). The drug was administered to the lenses using an immersion technique, and the process parameters were monitored to control drug release efficiency and profile. The drug release was measured in an Artificial Lacrimal Fluid (ALF) buffer, mimicking tear fluid with a pH of 7.9. The stability of CyA in this buffer was assessed. For the parameters used, the best drug application and release profile was achieved by immersing the contact lenses for 24 hours at 25 °C in a CyA solution containing 20 μg/ml of the active substance and adding 5 mg/ml of Vitamin E.

Recent Advancement in Ocular Drug Delivery System: A Systematic Review

Recent scientific and technological advancements have made ophthalmology a top priority for the study of therapeutic products, including the creation, preclinical testing, and clinical evaluation of novel medications, medical devices, and drug-medical device combinations. In order to decrease metabolism and elimination and increase residence time in ocular tissues and compartments, sustained-release drug delivery systems such as liposomes, micelles, nano-emulsions, nanoparticles with colloidal structures, and intraocular implants have been developed. Research is also being conducted in the area of cutting-edge medicines, including those based on gene or cell systems, both of which are considered high-risk products because to their intricate structures. Regarding the definition of drug (medicinal product) and recent changes in regulation, this article reviews recent advancements in ophthalmic drug, gene, and cellular delivery systems and related goods as well as breakthroughs in advanced therapeutic medicinal Products.

Therapeutic applications of contact lens-based drug delivery systems in ophthalmic diseases

Traditional ophthalmic drugs, such as eye drops, gels and ointments, are accompanied by many problems, including low bioavailability and potential drug side effects. Innovative ophthalmic drug delivery systems have been proposed to overcome the limitations associated with traditional formulations. Recently, contact lens-based drug delivery systems have gained popularity owing to their advantages of sustained drug delivery, prolonged drug retention, improved bioavailability, and few drug side effects. Various methods have been successfully applied to drug-loaded contact lenses and prolonged the drug release time, such as chemical crosslinking, material embedding, molecular imprinting, colloidal nanoparticles, vitamin E modification, drug polymer film/coating, ion ligand polymerization systems, and supercritical fluid technology. Contact lens-based drug delivery systems play an important role in the treatment of multifarious ophthalmic diseases. This review discusses the latest developments in drug-loaded contact lenses for the treatment of ophthalmic diseases, including preparation methods, application in ophthalmic diseases and future prospects.

In situ gels: The next new frontier in ophthalmic drug delivery system

AbstractRecently, the eye drug delivery system has received increasing attention. The in situ ophthalmic gel is a semisolid ophthalmic preparation that can be changed in the eyes immediately after the solution is administered, showing unique advantages as a new drug delivery system. Although there are still some problems to be solved, the in situ ophthalmic gel is a promising drug delivery system to treat ocular diseases, due to its properties in improving the bioavailability, prolonging the retention time of the drug, producing a sustained‐release effect, and possessing little toxicity and irritation. In this review, the characteristics, classification, ocular barrier, and route of administration of in situ ophthalmic gel have been introduced in detail for expanding the horizon of nanoscale technologies in the treatment of ocular diseases in the foreseeable future.

Comparative study of cyclosporine A liposomes and emulsions for ophthalmic drug delivery: Process optimization through response surface methodology (RSM) and biocompatibility evaluation

Herein, cyclosporine A loaded liposomes (CsA-Lips) were fabricated aimed at improving the biocompatibility of the ophthalmic formulation and getting rid of the direct contact of ocular tissues with irritant excipients. Response surface methodology was exploited in order to investigate the influence of miscellaneous factors on the key characteristics of CsA-Lips. Ratio of EPC:CsA, ratio of EPC:Chol, and stirring speed were selected as the independent variables, while size, drug-loading content (DL), and drug-loading content (DL) loss rate were applied as the response variables. In case of the maximal lack-of-fit p-value and minimum sequential p-value, quadratic model was regarded as the fittest model to analyze the data. The correlation of independent variables with response variables was described by three-dimension surface figures. Optimized formulation for CsA-Lips was obtained with ratio of EPC:CsA set as 15, ratio of EPC:Chol set as 2, and stirring speed set as 800 rpm. The particle size of CsA-Lips was 129.2 nm after optimalization while their TEM images exhibited spherical unilamellar vesicles with clearly shell-core structure. CsA released more rapidly from CsA-Lips in comparison with self-made emulsion and Restasis®. Besides, minimum cytotoxicity of CsA-Lips was perceived via both MTT method and LDH method, indicating the excellent compatibility of the ophthalmic formulation. Simultaneously, CsA-Lips showed enhanced nonspecific internalization in the cytoplasm with a time-dose-dependent manner. In conclusion, CsA-Lips could be adhibited as the hopeful ophthalmic drug delivery system clinically for dry eye syndrome (DES).

Research progress of ophthalmic preparations of immunosuppressants

Immune ophthalmopathy is a collection of autoimmune eye diseases. Immunosuppressants are drugs that can inhibit the body’s immune response. Considering drug side effects such as hepatorenal toxicity and the unique structure of the eye, incorporating immunosuppressants into ophthalmic nanodrug delivery systems, such as microparticles, nanoparticles, liposomes, micelles, implants, and in situ gels, has the advantages of improving solubility, increasing bioavailability, high eye-target specificity, and reducing side effects. This study reviews recent research and applications of this aspect to provide a reference for the development of an ophthalmic drug delivery system.

Intraocular delivery considerations of ocular biologic products and key preclinical determinations

Introduction Ophthalmic diseases of the retina are a significant cause of vision loss globally. Despite much progress, there remains an unmet need for durable, long-acting treatment options. While biologic therapies show great promise, they present many challenges, including complexities in biochemical properties, mechanism of action, manufacturing considerations, preclinical evaluation, and delivery mechanism; these are confounded by the unique anatomy and physiology of the eye itself. Areas covered This review describes the current development status of intravitreally administered drugs for the treatment of ophthalmic disease, outlines the range of approaches that can be considered for sustained drug delivery to the eye, and discusses key preclinical considerations for the evaluation of ocular biologics. Expert opinion The required frequency of dosing in the eye results in a great burden on both patients and the health care system, with direct intraocular administration remaining the most reliable and predictable route. Sustained and controlled ophthalmic drug delivery systems will go a long way in reducing this burden. Sustained delivery can directly dose target tissues, improving bioavailability and reducing off-target systemic effects. Maintaining stability and activity of compounds can prevent aggregation and enable extended duration of release, while sustaining dosage and preventing residual polymer after drug depletion.

OCULAR DRUG DELIVERY SYSTEMS: AN OVERVIEW

The treatment for the ophthalmic diseases are topical route because of the various ocular barrier. Ocular drug delivery systems are considered as major challenges by today’s pharmacologist and formulation scientist. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery techniques, which may surpass these barriers and maintain drug levels in tissues. There are many eye ailments which affected to eye and one can loss the eye sight also. Therefore, many ophthalmic drug delivery systems are available. These are classified as conventional and non- conventional (newer) drug delivery systems. Most commonly available ophthalmic preparations are eye drops and ointments about 70% of the eye dosage formulations in market. So overcome to these problems newer pharmaceutical ophthalmic formulation such as in-situ gel, nanoparticle, liposome, nanosuspension, microemulsion, intophoresis and ocular inserts have been developed in last three decades increase the bioavailability of the drug as a sustained and controlled manner.