Ophthalmic Nanoemulsion Fingolimod Formulation for Topical Application.

Purpose: Fingolimod (FTY720; FT), a structural analog of sphingosine, has potential ocular applications. The goal of this study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. Methods: FT-NE formulations were prepared using homogenization followed by the probe sonication method. The lead FT-NE formulations (0.15% and 0.3% w/v loading), comprising soybean oil as oil and Tween® 80 and Poloxamer 188 as surfactants, were further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. Ocular bioavailability following topical application of FT-NE (0.3%) was examined in Sprague-Dawley rats. Results: The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature postfiltration through a polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release over 24 h, compared with the control FT solution (FT-S). In vivo studies revealed that effective concentrations of FT were achieved in the vitreous humor and retina following topical application of FT-NE. Conclusions: The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196 nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.

Mechanism of Ocular Penetration of Lipophilic Drugs from Lipophilic Vehicles.

Since eyedrops have conventionally been formulated in aqueous vehicles, ocular pharmacokinetic studies are generally performed using aqueous buffers to identify physicochemical properties of the drug and the vehicles that influence drug absorption. In recent years, biocompatible lipophilic vehicles are increasingly finding application in ocular drug delivery; however, the mechanism of drug penetration from these non-aqueous vehicles is poorly understood. This study aims to compare ocular penetration of the model lipophilic drug curcumin when incorporated into lipophilic vehicles. To elucidate whether intrinsic solubility in the lipophilic vehicle influences ocular penetration, a curcumin solution and suspension were prepared in medium chain triglycerides (MCT) and squalane, respectively. Ocular penetration and distribution of curcumin from both vehicles was compared and evaluated qualitatively and quantitatively ex vivo. Significantly greater and faster penetration was observed from the squalane suspension than from the MCT solution in all ocular tissues. Our results suggest that the ability of lipophilic drugs to partition out of lipophilic vehicles and into cell membranes, rather than their intrinsic solubility in the lipophilic vehicle, determines the rate and extent of their ocular penetration.

Biopolymeric Innovations in Ophthalmic Surgery: Enhancing Devices and Drug Delivery Systems.

The interface between material science and ophthalmic medicine is witnessing significant advances with the introduction of biopolymers in medical device fabrication. This review discusses the impact of biopolymers on the development of ophthalmic devices, such as intraocular lenses, stents, and various prosthetics. Biopolymers are emerging as superior alternatives due to their biocompatibility, mechanical robustness, and biodegradability, presenting an advance over traditional materials with respect to patient comfort and environmental considerations. We explore the spectrum of biopolymers used in ophthalmic devices and evaluate their physical properties, compatibility with biological tissues, and clinical performances. Specific applications in oculoplastic and orbital surgeries, hydrogel applications in ocular therapeutics, and polymeric drug delivery systems for a range of ophthalmic conditions were reviewed. We also anticipate future directions and identify challenges in the field, advocating for a collaborative approach between material science and ophthalmic practice to foster innovative, patient-focused treatments. This synthesis aims to reinforce the potential of biopolymers to improve ophthalmic device technology and enhance clinical outcomes.

Recent updates on ocular disease management with ophthalmic ointments.

Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical and systemic treatments are preferred to address these sight-threatening conditions. However, the unique anatomy of the eye presents challenges for drug delivery. Various ophthalmic ointment formulations have been developed to enhance bioavailability in the eye to prolong residence time and improve corneal permeability. This article explores a wide range of ocular diseases affecting individuals globally and how ointments are used to manage them. From eye to ocular barriers, this review focuses on published scientific research and formulation strategies for severe ocular complications using conventional topical ointments. Additionally, it delves through patented technologies and marketed formulations supporting the use of ointments in ocular drug delivery.

Eye illnesses can cause blindness. The treatment is tricky due to eye's complex makeup. This paper talks about eye ointments also known as 'creams' or 'pomades' used to deliver medicine to the eye. These creams make the medicine work better by staying in the eye longer and absorbing faster. The present work looks at different eye problems and talks about ointments used to treat both internal and external eye diseases. It also explains how the eye is built and why it is hard for medicine to get in. There is also an information about ointments that have been discovered with some new ideas and those available in the market to cure eye problems.

Improving corneal permeability of dexamethasone using penetration enhancing agents: First step towards achieving topical drug delivery to the retina.

With an ever-increasing burden of vision loss caused by diseases of the posterior ocular segment, there is an unmet clinical need for non-invasive treatment strategies. Topical drug application using eye drops suffers from low to negligible bioavailability to the posterior segment as a result of static and dynamic defensive ocular barriers to penetration, while invasive delivery systems are expensive to administer and suffer potentially severe complications. As the cornea is the main anatomical barrier to uptake of topically applied drugs from the ocular surface, we present an approach to increase corneal permeability of a corticosteroid, dexamethasone sodium-phosphate (DSP), using a novel penetration enhancing agent (PEA). We synthesised a novel polyacetylene (pAc) polymer and compared its activity to two previously described cell penetrating peptide (CPP) based PEAs, TAT and penetratin, with respect to increasing transcorneal permeability of DSP in a rapid ex-vivo porcine corneal assay over 60 min. The transcorneal apparent permeability coefficients (Papp) for diffusion of pAc, and fluorescein isothiocyanate (FITC) conjugated TAT and penetratin were up to 5 times higher (p < 0.001), when compared to controls. When pAc was used in formulation with DSP, an almost 5-fold significant increase was observed in Papp of DSP across the cornea (p = 0.0130), a significant 6-fold increase with TAT (p = 0.0377), and almost 7-fold mean increase with penetratin (p = 0.9540). Furthermore, we investigated whether the PEAs caused any irreversible damage to the barrier integrity of the corneal epithelium by measuring transepithelial electrical resistance (TEER) and immunostaining of tight junction proteins using zonula occludens-1 (ZO-1) and occludin antibodies. There was no damage or structural toxicity, and the barrier integrity was preserved after PEA application. Finally, an in-vitro cytotoxicity assessment of all PEAs in human retinal pigment epithelium cells (ARPE-19) demonstrated that all PEAs were very well-tolerated, with IC50 values of 64.79 mM for pAc and 1335.45 µM and 87.26 µM for TAT and penetratin, respectively. Our results suggest that this drug delivery technology could potentially be used to achieve a significantly higher intraocular therapeutic bioavailability after topical eye drop administration, than currently afforded.

Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma.

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Antioxidant Carbon Dots Nanozyme Loaded in Thermosensitive in situ Hydrogel System for Efficient Dry Eye Disease Treatment.

Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.

Ocular RNA nanomedicine: engineered delivery nanoplatforms in treating eye diseases.

Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy.

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study.

The transcorneal route is the main entry route for drugs to the intraocular parts, after topical administration. The outer surface, the corneal epithelium (CE), forms the rate-limiting barrier for drug permeability. Information about the role and protein expression of drug and amino acid transporter proteins in the CE is sparse and lacking. The aim of our study was to characterize transporter protein expression in rabbit and porcine CE to better understand potential drug and nutrient absorption after topical administration. Proteins, mainly Abc and Slc transporters, were characterized with quantitative targeted absolute proteomics and global untargeted proteomics methods. In the rabbit CE, 24 of 48 proteins were detected in the targeted approach, and 21 of these were quantified. In the porcine CE, 26 of 58 proteins were detected in the targeted approach, and 20 of these were quantified. Among these, 15 proteins were quantified in both animals: 4f2hc (Slc3a2), Aqp0, Asct1 (Slc1a4), Asct2 (Slc1a5), Glut1 (Slc2a1), Hmit (Slc2a13), Insr, Lat1 (Slc7a5), Mct1 (Slc16a1), Mct2 (Slc16a7), Mct4 (Slc16a3), Mrp 4 (Abcc4), Na+/K+-ATPase, Oatp3a1 (Slco3a1), and Snat2 (Slc38a2). Overall, the global proteomics results supported the targeted proteomics results. Organic anion transporting polypeptide Oatp3a1 was detected and quantified for the first time in both rabbit (1.4 ± 0.4 fmol/cm2) and porcine (11.1 ± 5.3 fmol/cm2) CE. High expression levels were observed for L-type amino acid transporter, Lat1, which was quantified with newly selected extracellular domain peptides in rabbit (48.9 ± 11.8 fmol/cm2) and porcine (37.6 ± 11.5 fmol/cm2) CE. The knowledge of transporter protein expression in ocular barriers is a key factor in the successful design of new ocular drugs, pharmacokinetic modeling, understanding ocular diseases, and the translation to human.

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics.

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.

Development of a biodegradable polymer-based implant to release dual drugs for post-operative management of cataract surgery.

Cataract surgery is followed by post-operative eye drops for a duration of 4-6 weeks. The multitude of ocular barriers, coupled with the discomfort experienced by both the patient and their relatives in frequently administering eye drops, significantly undermines patient compliance, ultimately impeding the recovery of the patient. This study aimed to design and develop an ocular drug delivery system as an effort to achieve a drop-free post-operative care after cataract surgery. An implant was prepared containing a biodegradable polymer Poly-lactic-co-glycolic acid (PLGA), Dexamethasone (DEX) as an anti-inflammatory drug, and Moxifloxacin(MOX) as an antibiotic. Implant characterization and drug loading analysis were conducted. In vitro drug release profile showed that the release of the two drugs are correlated with the clinical prescription for post operative eye drops. In vivo study was conducted on New Zealand albino rabbits where one eye underwent cataract surgery, and the drug delivery implant was inserted into the capsular bag after placement of the synthetic intraocular lens (IOL). Borderline increase in the intraocular pressure (IOP) was noted in the test sample group. Slit-lamp observations revealed no significant anterior chamber reaction in all study groups. Histopathology study of the operated eye revealed no significant pathology in the test samples. This work aims at developing the intra ocular drug delivery implant which will replace the post-operative eye drops and help the patient with the post-operative hassle of eye drops.

Developing a synergistic rate-retarding polymeric implant for controlling monoclonal antibody delivery in minimally invasive glaucoma surgery.

Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive glaucoma surgeries. Here, by controlling mAb passive diffusion, we developed a polymeric, rate-controlling membrane reservoir loaded with poly(lactic-co-glycolic acid) microspheres to deliver mAb for several weeks. Different parameters were tested to ensure that the microspheres achieved a good quality characteristic, and our results showed that 1 %W/V emulsifier with 5 %W/V NaCl achieved mAb-loaded microspheres with the highest stability, encapsulation efficiency and minimal burst release. Then, we fabricated and compared 10 types of microporous films based on polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG). Our results revealed distinct pore characteristics and degradation patterns in different films due to varying polymer properties, and all the polymeric film formulations showed good biocompatibility in both human trabecular meshwork cells and human conjunctival fibroblasts. Finally, the optimized microspheres were loaded into the reservoir-type polymeric implant assembled by microporous membranes with different surface coating modifications. The implant formulation, which was fabricated by 60 PCL: 40 PEG (3 %W/V) polymer with 0.1 %W/V poly(lactic-co-glycolic acid) barrier, exerted the best drug release profile that can sustained release mAb (83.6 %) for 4 weeks.

Nanoemulsion Carriers for Ocular Fungal Infection: Main Emphasis on Keratomycosis.

Keratomycosis, also termed fungal keratitis (FK), is an invasive eye condition for which there is a lack of available effective treatment due to pharmacological shortages and vital ocular obstacles. This severe corneal infection typically suppurates and eventually ulcerates, ultimately causing blindness or decreased vision. According to epidemiological studies, FK is more common in warm, humid places with an agricultural economy. The use of nanoemulsion carriers for ocular fungal infection has been promoting better treatment and patient compliance. The persistent fungal infection like FK, affecting particularly the stroma heralds complications thereby posing difficulty in diagnosis and treatment. To help treat refractory cases and improve outcomes, recently targeted drug delivery techniques and novel antifungal drugs shall be explored. A delay in diagnosis may cause corneal fungal infections to have irreversible consequences, which cannot be avoided. However, infections can develop into ocular perforation even after receiving intense care. The commonly used chemotherapy for FK is based on topical (natamycin 5% is typically first-line therapy) and systemic administration of azole drugs. To address the problems related to better treatment, various nanoemulsion carriers were discussed. Novel drug delivery systems based on nanoemulsions are a viable therapeutic option for treating keratomycosis and may be a candidate method for overcoming obstacles in the treatment of many other ocular illnesses when combined with different hydrophobic medicines. With a brief explanation of the pathogenesis, this article seeks to give readers a thorough analysis of current trends, various treatment choices, and care strategies for fungal keratitis.

Optimization of stereolithography 3D printing of microneedle micro-molds for ocular drug delivery.

Microneedles (MN) have emerged as an innovative technology for drug delivery, offering a minimally invasive approach to administer therapeutic agents. Recent applications have included ocular drug delivery, requiring the manufacture of sub-millimeter needle arrays in a reproducible and reliable manner. The development of 3D printing technologies has facilitated the fabrication of MN via mold production, although there is a paucity of information available regarding how the printing parameters may influence crucial issues such as sharpness and penetration efficacy. In this study, we have developed and optimized a 3D-printed MN micro-mold using stereolithography (SLA) 3D printing to prepare a dissolving ocular MN patch. The effects of a range of parameters including aspect ratio, layer thickness, length, mold shape and printing orientation have been examined with regard to both architecture and printing accuracy of the MN micro-mold, while the effects of printing angle on needle fidelity was also examined for a range of basic shapes (conical, pyramidal and triangular pyramidal). Mechanical strength and in vitro penetration of the polymeric (PVP/PVA) MN patch produced from reverse molds fabricated using MN with a range of shapes and height, and aspect ratios were assessed, followed by ex vivo studies of penetration into excised scleral and corneal tissues. The optimization process identified the parameters required to produce MN with the sharpest tips and highest dimensional fidelity, while the ex vivo studies indicated that these optimized systems would penetrate the ocular tissue with minimal applied pressure, thereby allowing ease of patient self-administration.

A sterilizable platform based on crosslinked xanthan gum for controlled-release of polymeric micelles: Ocular application for the delivery of neuroprotective compounds to the posterior eye segment.

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release. The system was loaded with melatonin and cyclosporin A, neuroprotective compounds to be delivered to the posterior eye segment. Citric acid and heating at different times and temperatures were exploited as crosslinking approach, giving the possibility to tune swelling, micelles release and drug release. The biocompatibility of the platform was confirmed by HET-CAM assay. Ex vivo studies on isolated porcine ocular tissues, conducted using Franz cells and two-photon microscopy, demonstrated the potential of the xanthan gum-based platform and enlightened micelles penetration mechanism. Finally, the sterilization step was approached, and a process to simultaneously crosslink and sterilize the platform was developed.

Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.

A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.