Posterior segment eye diseases represent the leading causes of vision impairment and blindness globally. Current therapies still have notable drawbacks, including the need for frequent invasive injections and the associated risks of severe ocular complications. Recently, the utility of external stimuli, such as light, ultrasound, magnetic field, and electric field, has been noted as a promising strategy to enhance drug delivery to the posterior segment of the eye. In this review, we briefly summarize the main physiological barriers against ocular drug delivery, focusing primarily on the recent advancements that utilize external stimuli to improve treatment outcomes for posterior segment eye diseases. The advantages of these external stimuli-responsive drug delivery strategies are discussed, with illustrative examples highlighting improved tissue penetration, enhanced control over drug release, and targeted drug delivery to ocular lesions through minimally invasive routes. Finally, we discuss the challenges and future perspectives in the translational research of external stimuli-responsive drug delivery platforms, aiming to bridge existing gaps toward clinical use.

Intracameral injection is a widely used surgical technique in animal research, serving various purposes such as injecting microbeads to establish a glaucoma model, delivering adeno-associated virus (AAV) to transduce the trabecular meshwork or corneal endothelium, and administering drugs into the anterior chamber. However, performing intracameral injections in mice is particularly challenging due to the small size of the eye and the shallow anterior chamber. To prevent leakage of injected substances, traditional methods often involve the co-injection of sterile air or viscous agents. However, these approaches have significant drawbacks, including the need for repeated injections and the risk of repeated corneal injuries. To address these limitations, we developed a simplified intracameral injection technique for mice that minimizes tissue damage. In this method, the needle first enters the posterior chamber before passing through the pupil into the anterior chamber. To validate the efficacy and safety of this technique, we used it to deliver AAV into the anterior chamber for corneal endothelial cell transduction and to inject magnetic microbeads for establishing a glaucoma model. Our results demonstrate that this novel method is effective, reproducible, and associated with fewer complications.

Fungal keratitis (FK) is a severe infectious corneal disease and a common cause of blindness. At present, natamycin (NATA) is the most commonly prescribed drug for fungal keratitis. However, these disadvantages, including poor water solubility, poor stability, and significant corneal irritation, limit its effect in clinical application. In this study, we innovatively prepare platelet membranes (PLTm) which are a unique population of cellular fragments that adhere to a variety of pathogens camouflaged with fabulous biocompatibility poly (lactic-co-glycolic acid) (PLGA) loaded NATA. PLTm can help NATA adhere to the fungal surface, increase the ocular surface retention, and achieve a double sustained-release effect, significantly increasing the antifungal effect of NATA. And platelet membrane-camouflaged PLGA loaded NATA (PLTm@PLGA-NATA) has better antifungal ability. Compared with pure NATA, PLTm@PLGA-NATA significantly improved the therapeutic effect on FK in vivo experiments. Moreover, in vitro, platelet membrane-camouflaged PLGA (PLTm@PLGA) can exert anti-inflammatory effects by reducing inflammatory cytokines caused by fungal stimulation. Therefore, this study provides a therapeutic strategy with a novel antifungal drug delivery system (DDS). Platelet membrane biomimetic nanoparticles play a promising role in treating FK.

Nanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions. Additionally, advanced nanodevices facilitate real-time monitoring and controlled drug release, marking significant progress in retinal therapy. This study reviews recent advancements in nanomedicine for retinal drug delivery, critically analysing design innovations, therapeutic benefits, and limitations of these systems. By advancing nanotechnology integration in ocular therapies, this field holds strong potential for overcoming current barriers, ultimately improving patient outcomes and quality of life.

This work aimed to prepare Terconazole loaded proniosomes (TCZ-PNS) utilizing modified coacervation technique for the management of fungal keratitis. Terconazole (TCZ) is a potent antifungal with poor aqueous solubility posing intricacies in its incorporation in ocular formulations. A 23 factorial design was adopted to probe independent formulation variables including A: Lecithin: cholesterol ratio, B: Surfactant: cholesterol ratio and C: Span® 80 contribution (% of total SAA). The formulae, generated by the design, were prepared and scrutinized regarding entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). Numerical desirability algorithms selected an optimum TCZ-PNS which boasted plausible %EE (89.51 % ± 0.94 %), nanoscale vesicles consistent with TEM measurements (247.9 ± 0.42 nm), a sufficiently high ZP (-43.42 ± 0.85 mV), and an in-vitro biphasic release profile that remained stable even after Gamma irradiation and short-term storage. The transcorneal ex-vivo permeation of TCZ-PNS was higher than that of TCZ suspension (≈ 2-fold). The formulation was further evaluated for pH, corneal hydration threshold, and histopathological safety, confirming its suitability for ocular application. Confocal laser microscopy revealed substantial corneal uptake (approximately twice as deep as of TCZ suspension). Additionally, microbiological assessments of the optimal TCZ-PNS compared to TCZ suspension demonstrated an inhibition zone nearly 50 % larger, a significantly lower MIC and MFC (64-fold reduction), and enhanced biofilm inhibition activity across most tested concentrations. These findings suggest that TCZ-PNS could be a propitious treatment choice to deeply deliver antifungal therapy for the eradication of deeply rooted and inaccessible fungal keratitis.

The goal of this study was to develop dexamethasone-loaded tear-driven phase transition microemulsions (PTMEs) to effectively treat uveitis.

PTMEs were prepared using the oil titration method. Physicochemical parameters, in vitro release, and ocular irritation studies were performed. The in vivo study, total cell count, and total protein content were estimated on the rabbit eye model.

The study revealed that developed PTMEs had nanoglobule sizes, acceptable physicochemical properties, and prolonged drug release. Ex-vivo and in-vivo studies concluded that higher permeability and improved anti-inflammatory properties were observed for PTMEs compared to marketed formulation.

The prepared PTMEs showed a sustained release pattern and enhanced therapeutic effectiveness, making them a promising alternative to conventional eye drops for treating uveitis.

Herein, we investigated the preparation and characterization of Terconazole loaded edge-activated hybrid elastosome (TCN-EHE) adopting thin film hydration technique for the treatment of ocular mycosis. Terconazole (TCN) is a broad spectrum antimycotic agent suffering from sparse aqueous solubility impeding its use in ophthalmic preparations. The scrutinized formulation variables namely X1: Surfactant: Edge activator ratio (SAA: EA), X2: Pluronic® L121 contribution (% of total SAA) and X3: EA concentration (%w/v) were optimized adopting D-optimal design. Ten runs were prepared and characterized regarding their entrapment efficiency, particle size, polydispersity index and zeta potential. An optimized formula was generated, with high desirability, exhibited satisfactory entrapment efficiency, nanoscaled particle size aligning with TEM, plausible zeta potential and bi-phasic release pattern which were not altered after short-term storage. The optimized TCN-EHE displayed 1.94-fold enhanced ex-vivo corneal permeation flux. Safety was ratified through measured corneal hydration level, pH and histopathological evaluation. In-vivo corneal uptake visualized by confocal laser microscopy demonstrated 2.7-fold deeper penetration. Moreover, Superior antifungal activity has been demonstrated displaying 37 % bigger zone of inhibition, 8-fold lower minimum inhibitory and minimum fungal concentration alongside significantly higher biofilm inhibition activity at all tested concentrations for the optimized TCN-EHE compared to TCN suspension. Conclusively, we could prospect that TCN-EHE might be a revamped therapeutic alternative for the delivery of poorly soluble antimycotic agents for the combat of ocular mycosis.

Glaucoma is an optic neuropathy in which progressive degeneration of retinal ganglion cells and the optic nerve leads to irreversible visual loss. Glaucoma is one of the leading causes of blindness. The pathogenesis of glaucoma is determined by different pathogenetic mechanisms, including increased intraocular pressure, mechanical stress, excitotoxicity, resistance to aqueous drainage and oxidative stress. Topical formulations are often used in glaucoma treatment, whereas surgical measures are used in acute glaucoma cases. For most patients, long-term glaucoma treatments are given. Poor patient compliance and low bioavailability are often associated with topical therapy, which suggests that sustained-release, long-acting drug delivery systems could be beneficial in managing glaucoma. This review summarizes the eye's physiology, the pathogenesis of glaucoma, current treatments, including both pharmacological and nonpharmacological interventions, and recent advances in long-acting drug delivery systems for the treatment of glaucoma.

Antibiotic eyedrops typically require frequent instillation due to the eye's defensive mechanisms limiting drugs from reaching target sites. This may risk patient non-adherence and treatment inefficacy. The aim of this study was to develop a biocompatible and fully soluble ocular film insert to enhance the delivery of levofloxacin, as well as the handling procedure for its administration; based on the anatomical dimensions and physiological conditions of the human eye. Inserts were prepared by solvent casting method, using HPMC, sodium alginate, gelatin, PEG 400, and levofloxacin solution, and characterised for various physicochemical properties (e.g., uniformity of weight and thickness, loss on dryness, swelling index, water uptake and surface pH). Mechanical properties were assessed and compared against a commercially available buccal film formulation. Uniformity of content and release profile of inserts were assessed by means of a validated analytical method. Antibacterial effectiveness was studied by adapted disc diffusion method on Staphylococcus aureus and Pseudomonas aeruginosa. The formulation including HPMC E15 (1250 mg), low viscosity sodium alginate (750 mg), type A gelatin (250 mg) and PEG 400 (2.5 mL) and 0.1% levofloxacin solution, resulted in high quality inserts, exhibiting uniformity of mass, thickness, and levofloxacin content, that comply with Pharmacopeial standards. Inserts were able to withstand unilinear and repeated mechanical stresses, suggesting suitability for manipulation linked to eye administration. The fully soluble levofloxacin-loaded inserts exhibited good physicochemical and mechanical characteristics, indicating good compatibility with ocular environment and administration procedure. Consistent levofloxacin content and biphasic release pattern showed immediate and sustained antimicrobial efficacy, consistently above the minimum inhibitory concentrations for the model species tested. This work also presents an experimental framework that can be adapted for designing and testing ocular drug delivery systems accounting for anatomical and physiological characteristics of the eye.

While transfersomes (TFS) have extensively been investigated as carriers for topical drug delivery to the skin, their application in ocular drug delivery remains largely unexplored. This study aimed to evaluate the tolerability, contact angle, and ocular penetration of tonabersat-loaded TFS using ex vivo models, with a focus on comparing drug distribution in different ocular tissues. A solution of tonabersat in medium chain triglycerides (MCT) was used as the control. Conjunctival tolerability was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), while the Bovine Corneal Opacity and Permeability (BCOP) assay was used to establish corneal tolerability. Drop contact angle on freshly excised bovine corneas was measured using a goniometer. Drug penetration into the cornea, conjunctiva, eyelid and sclera-choroid was evaluated using an ex vivo porcine whole eye model under simulated tear flow, 0.25, 0.5, 1, and 2 h after eyedrop application. Both the TFS and MCT formulations exhibited good conjunctival and corneal tolerability with the TFS contact angle on the corneal surface being lower than that of MCT. Significantly greater drug concentrations were achieved in all ocular tissues with the TFS eyedrop, with the Cmax from TFS being at least 16-fold higher than that achieved with the MCT solution in the conjunctiva, eyelid and sclera-choroid, with the difference being greatest in the latter. Meanwhile, the corneal Cmax was 6-fold greater with TFS. Interestingly, despite simulated tear flow, the Tmax was observed at a later timepoint with TFS in all ocular tissues. Overall, this study demonstrates that TFS are well tolerated on the ocular surface and have the potential for sustained and targeted drug delivery to ocular tissues. Thus, they present a promising alternative for safe and effective ocular drug delivery.

The eye is a complex organ with several anatomical and physiological barriers that make ocular drug delivery an ongoing challenge. Transfersomes (TFS) are deformable vesicles that have been extensively applied to enhance transdermal drug delivery. However, their application in ocular drug delivery remains largely unexplored.

This review highlights the challenges typically associated with ocular drug delivery and emphasizes the inherent properties of TFS that enable them to overcome these challenges. The influence of excipients and critical process parameters on TFS characteristics have been discussed in detail with an emphasis on the fabrication and characterization techniques typically employed for TFS development and optimization. Furthermore, recent studies evaluating the application of TFS in ocular drug delivery have been discussed in depth.

The unique stress-responsive and deformable nature of TFS makes them promising carriers for ocular drug delivery. However, further research in this direction is needed to understand their penetration mechanism and elucidate their potential for sustained and targeted drug delivery to ocular tissues. Moreover, further research is needed to optimize the stability and scalability of TFS to encourage their translation to the market.

Ocular drug delivery is a significant challenge due to the intricate anatomy of the eye and the various physiological barriers. Conventional therapeutic approaches, while effective to some extent, often fall short in effectively targeting ocular diseases, resulting in suboptimal therapeutic outcomes due to factors such as poor ocular bioavailability, frequent dosing requirements, systemic side effects, and limited penetration through ocular barriers. This review elucidates the eye's intricate anatomy and physiology, prevalent ocular diseases, traditional therapeutic modalities, and the inherent pharmacokinetic and pharmacodynamic limitations associated with these modalities. Subsequently, it delves into nanotechnology-based solutions, presenting breakthroughs in nanoformulations such as nanocrystals, liposomes, dendrimers, and nanoemulsions that have demonstrated enhanced drug stability, controlled release, and deeper ocular penetration. Additionally, it explores a range of nanosized carriers, including nano-structured lipid carriers, hydrogels, nanogels, nanoenzymes, microparticles, conjugates, exosomes, nanosuspensions, viral vectors, and polymeric nanoparticles, and their applications. Unique insights include emerging innovations such as nanowafers and transcorneal iontophoresis, which indicate paradigm shifts in non-invasive ocular drug delivery. Furthermore, it sheds light on the advantages and limitations of these nanotechnology-based platforms in addressing the challenges of ocular drug delivery. Though nano-based drug delivery systems are drawing increasing attention due to their potential to enhance bioavailability and therapeutic efficacy, the review ends up emphasizing the imperative need for further research to drive innovation and improve patient outcomes in ophthalmology.

This study aims to describe an innovative suprachoroidal space injection technique using a combination of 30 G and 22 G needles attached to a 1 ml injector. The efficacy and applicability of this technique in suprachoroidal injections are evaluated.

In this study, we conducted both in vitro and in vivo injection experiments using isolated porcine eyes and live SD rats, respectively. The injector needle was inserted into the sclera with the bevelled tip facing the sclera and parallel to the corneal limbus, and the methylene blue solution was injected into the suprachoroidal space. The accuracy of the injection was confirmed by OCT imaging and frozen section microscopy, demonstrating that the dye was successfully delivered to the suprachoroidal space.

The suprachoroidal injector successfully injected the solution into the suprachoroidal space of isolated porcine eyes and live rats without entering the vitreous cavity.

The 22 G needle demonstrated sufficient rigidity and stability to ensure proper scleral compression, supporting the consistency of the injection depth. The 30 G needle exhibited exceptional sharpness and precision, allowing for more accurate control of the drug dosage. The appropriate force applied to the sclera facilitated the precise depth of injection. The angle of the needle, parallel to the corneal limbus, helped avoid penetration into the vitreous or subretinal space, reducing the risk of complications. This device offers new tools and methods for ophthalmic research and clinical practice, with significant clinical application prospects.

The corneal complications can result in opacity and eventual blindness. Furthermore, a shortage of available donors constrains the existing therapeutic options. Therefore, one of the most promising strategies involves the application of biomaterials, particularly silk. Silk has garnered significant attention among these biomaterials due to its natural origin and diverse features derived from different sources. One of the most critical factors of silk is its transparency, which is crucial for the cornea, and there are no concerns about infection. This material also possesses several advantages, including cost-effectiveness in production, biocompatibility in vivo and in vitro, biodegradation, and desirable mechanical characteristics. Modifications in the topographical structure, porosity, and crystallinity of silk enhance its properties and optimize its suitability for wound dressing, efficient drug delivery systems, and various cornea-related treatments. In each layer, silk was examined as a single biomaterial or blended with the others, so, this review aims to explore silk as a potential material for corneal regenerative medicine from a novel viewpoint. By considering a range of studies, a classification system has been developed that categorizes the utilization of silk in the various layers of the cornea and sub-categorizes the different modifications and applications of silk.

Retinal diseases are a leading cause of vision loss, affecting millions of people worldwide. Current treatment options are based on invasive methods such as intravitreal injections. Therefore, there is a need for alternative therapeutic strategies that are both effective and more patient-friendly.

Topical drug delivery has gained attention as a preferred noninvasive approach, although it is hindered by several ocular barriers. Cyclodextrin (CD)-based nanoparticles have emerged as a promising strategy to overcome these limitations by enhancing drug permeability in the posterior segment of the eye. This review discusses the potential of CDs as enabling pharmaceutical excipients, their role in improving ocular drug bioavailability, and provides examples of CD-based eye drop formulations currently under development or undergoing clinical trials. Also, the role of CDs as active pharmaceutical agents in ophthalmology is discussed.

CD-based nanoparticle eye drops present a promising solution and have shown clinical success. CDs are approved pharmaceutical excipients for eye drop formulations and can act as active pharmaceutical ingredients for the treatment of inherent retinal diseases. Future innovations in hybrid CD-based delivery systems and integration of novel therapeutic compounds could provide more efficient and targeted treatment options for retinal diseases.

Ocular nanogels have emerged as a promising therapeutic approach, and nanotechnology has speed up the growth of the pharmaceutical and medical technology sectors. The physiological and anatomical barriers of the eye limit the use of traditional ocular preparations, which leads to low drug bioavailability and a brief retention period. This presents a serious problem for patients, doctors, and chemists. Nevertheless, nanogels can encapsulate medications within three-dimensional crosslinked polymeric networks and provide controlled and prolonged drug delivery by using particular structural layouts and unique preparation techniques, improving therapeutic efficacy and patient compliance. Dextran and its variants, a naturally occurring polysaccharide, have drawn a lot of interest in developing delivery systems for use in pharmaceutical and medical applications. Many dextran-based delivery systems with customized geometries and features have been fabricated recently, such as hydrogels, nanogels, magnetic nanoparticles, nanoemulsions, self-assembled micelles and nanoparticles, and microparticles. The review presents advancement and therapeutic potential of dextran-based nanogels for the treatment of various eye conditions, such as cataract, conjunctivitis, glaucoma, dry eye syndrome, age-related macular degeneration, and corneal ulcers. Moreover, the process for development and assessing these nanomedicines, emphasizing their safety and effectiveness as established by preclinical, toxicological, clinical assessments, and patent updates, has been elaborated.

The integration of nanotechnology into drug delivery systems holds great promise for enhancing pharmaceutical effectiveness. This approach enables precise targeting, controlled release, improved patient compliance, reduced side effects, and increased bioavailability. Nanoparticles are vital for transporting biomolecules-such as proteins, enzymes, genes, and vaccines-through various administration routes, including oral, intranasal, vaginal, buccal, and pulmonary. Among biodegradable polymers, chitosan, a linear polysaccharide derived from chitin, stands out due to its biocompatibility, safety, biodegradability, mucoadhesive properties, and ability to enhance permeation. Its cationic nature supports strong molecular interactions and provides antimicrobial, anti-inflammatory, and hemostatic benefits. However, its solubility, influenced by pH and ionic sensitivity, poses challenges requiring effective solutions. This review explores chitosan, its modified derivatives and chitosan nanoparticles mainly, focusing on nanoparticles physicochemical properties, drug release mechanisms, preparation methods, and factors affecting their mean hydrodynamic diameter (particle size). It highlights their application in drug delivery systems and disease treatments across various routes. Key considerations include drug loading capacity, zeta potential, and stability, alongside the impact of molecular weight, degree of deacetylation, and drug solubility on nanoparticle properties. Recent advancements and studies underscore chitosan's potential, emphasizing its modified derivatives'versatility in improving therapeutic outcomes.

High intraocular pressure (IOP) is the main risk factor for glaucoma progression. Acetazolamide (AZM) presents a potent IOP-lowering effect but is only administered orally due to its low aqueous solubility and ocular permeability. This study aimed to develop AZM nanocrystals (AZM-NC) as an alternative for its topical ocular delivery. AZM-NC were obtained by wet bead milling technique followed by spray-drying, and a mixture design study was conducted to evaluate the optimal drug-to-stabilizer ratio regarding colloidal properties and stability. AZM-NC exhibited an average particle size of 299.7 ± 8.8 nm, a polydispersity index of 0.13 ± 0.01, and a zeta potential of -29.0 ± 0.9 mV, which remained mostly unchanged for at least 60 days when the dried powder was stored at room temperature. Fourier-transformed spectroscopy and powder X-ray diffraction analyses revealed no chemical or crystallinity changes in AZM-NC compared with AZM, respectively. Additionally, AZM-NC demonstrated increased drug saturation concentration, globular shapes, and higher adhesive properties than normal-sized AZM powder. Topical ocular administration of AZM-NC in albino male rabbits showed no clinical signs of ocular damage. Further, in vivo studies revealed a significant IOP reduction of up to 32 % of the basal IOP (-4.8 ± 1.2 mmHg, p < 0.05) in normotensive rabbit eyes (n = 7), after 4 h of AZM-NC suspension topical application, compared to groups treated with AZM suspension, normal saline solution and, AZOPT® (-1.8 ± 1.4 mmHg). Thus, AZM-NC could present a promising approach for developing an eye drop formulation for the localized management of glaucoma.

Keratoconjunctivitis sicca (KCS) is a common ocular disease in dogs characterized by inflammation of the cornea and conjunctiva. This study investigates the effectiveness of gelatin-epigallocatechin gallate nanoparticles with hyaluronic acid coating (GEH NPs) and various artificial tears in treating KCS led keratopathy in a rat model. Eighteen female Sprague-Dawley rats, aged 6 to 8 weeks were randomly assigned to 6 groups of 3. All rats except the Sham group underwent unilateral exorbital and infraorbital lacrimal gland excisions to induce KCS. The treatment groups included a KCS group without treatment, a GEH group treated with GEH NPs, and 3 groups receiving different artificial tears. Clinical examinations, including slit-lamp biomicroscopy, optical coherence tomography (OCT), and ocular surface analyser-VET (OSA-VET) were conducted preoperatively at 1 and 2 weeks postoperatively. For treating KCS associated keratopathy, the GEH NPs showed superior outcomes and consistently ranked among the strongest treatment options in most aspects evaluated, including reduced corneal irregularity, improved tear film stability, and lower fluorescein scores, indicating better corneal integrity. Additionally, the GEH group displayed the least inflammatory cell infiltration and maintained a healthier epithelial structure, further underscoring its protective effects. GEH was administered twice daily while other treatment groups were administrated 3 times daily, highlighting its efficacy even with a lower dosing frequency. The artificial tears demonstrated variable benefits on KCS led keratopathy across different evaluations. GEH NPs exhibited excellent protective effects and therapeutic potential on dry eye associated keratopathy based on this study.

Retinitis pigmentosa is a genetically heterogeneous retinal degeneration process. There is hardly any treatment available. It is associated with extensive chronic inflammation and the release of proinflammatory cytokines such as TNFα. The blockade of TNFα through systemic or intraocular routes slows retinal degeneration. They are invasive routes with possible side effects. Herein, we propose a noninvasive approach to address the inflammatory component of retinitis pigmentosa. This approach is based on the development of eye drops of nanostructured lipid carriers (NLCs) loaded with the monoclonal antibody against TNFα, adalimumab (ADA). We physicochemically characterized NLC-ADA. We evaluated retinal and corneal toxicity; corneal permeation; diffusion to the retina; and effects on retinal dysfunction, degeneration and inflammation. These results prove that NLC-ADA eye drops exhibit excellent corneal permeation, no toxicity and high retinal distribution in mice. These compounds improve retinal function, reduce retinal degeneration and ameliorate the inflammatory process. In particular, NLC-ADA eye drops reduce M1 microglial activation, macrophage infiltration and the levels of some components of the NLRP3 inflammasome in rd10 mice, a model of retinitis pigmentosa. This strategy offers a noninvasive route that circumvents the bloodretinal barrier in a safe and efficient manner. Hence, this approach could offer a promising therapeutic option for treating retinitis pigmentosa regardless of genetic defects. This approach could be useful for other inflammation-related retinal diseases.

Topical ophthalmic drug delivery targeting the posterior segment of the eye has become a key area of interest due to its non-invasive nature, safety, ease of application, patient compliance, and cost-effectiveness. However, achievement of effective drug bioavailability in the posterior ocular segment is a significant challenge due to unique ocular barriers, including precorneal factors and anatomical barriers, like the cornea, the conjunctiva, and the sclera. Successful ocular drug delivery systems require increased precorneal residence time and improved corneal penetration to enhance intraocular bioavailability. A promising strategy to overcome these barriers is incorporating drug penetration enhancers (DPEs) into formulations. These compounds facilitate drug delivery by improving permeability across otherwise impermeable or poorly permeable membranes. At the ocular level, they act through three primary mechanisms: breaking tear film stability by interfering with the mucous layer; disrupting membrane components such as phospholipids and proteins; and loosening epithelial cellular junctions. DPEs offer significant potential to improve bioavailability and therapeutic outcomes, particularly for drugs targeting the posterior segment of the eye. This review is focused on analyzing the current literature regarding the use of penetration enhancers in topical ocular drug delivery, highlighting their mechanisms of action and potential to revolutionize ophthalmic treatments.

The human eye is a highly intricate sensory organ. When a condition requiring treatment occurs, eyedrops, which represent 90% of all ophthalmic treatments, are most frequently used. However, eyedrops are associated with low bioavailability, with less than 0.02% of therapeutic molecules reaching the anterior chamber. Thus, new delivery systems are required to ensure sufficient drug concentration over time at the target site. Gold nanoparticles are a promising avenue for drug delivery; however, they can be difficult to track in biological systems. Fluorescent gold nanoparticles, which have the same ultrastability and biocompatibility as their nonfluorescent counterpart, could act as an effective imaging tool to study their localization throughout the eye after administration. Thus, this study (1) synthesized and characterized fluorescent gold nanoparticles, (2) validated similar properties between nonfluorescent and fluorescent gold nanoparticles, and (3) determined their localization in the eye after topical application on ex vivo rabbit eyes. The fluorescent gold nanoparticles were synthesized, characterized, and identified in the cornea, iris, lens, and posterior segment of rabbit eyeballs, demonstrating tremendous potential for future drug delivery research.

Managing Dry Eye Disease (DED), a prevalent condition affecting the ocular surface, remains challenging despite advancements in diagnostics and therapies. Current treatments primarily involve lubricating eye drops and anti-inflammatory medications, which often require prolonged use and generally provide only symptomatic relief. The current study focuses on improving DED treatments through nano-drug delivery technologies and advanced formulations. These systems aim to address the limitations of conventional therapies by providing extended, targeted, and sustained drug release. The development of innovative nanomaterials offers improved precision, control, and customization for DED management. By enabling controlled and sustained drug release, these nano-drug delivery systems could offer longer-lasting relief, addressing the chronic nature of DED more effectively than current symptomatic therapies. Future research should focus on integrating multiple therapeutic agents within these systems to simultaneously target inflammation and tear film instability. This review examines the potential of nano-based materials for DED treatment, with a particular emphasis on lipid-based, polymer-based and polysaccharide-based systems.

Conventional ocular drug delivery systems face challenges like rapid clearance, high dosages, low compliance, and poor bioavailability. A novel solution utilizes mucoadhesive polymers for controlled release, enhancing drug effectiveness while reducing dosages and frequency. Polymeric micelles, nanosized colloidal DDS, are set to modify drug delivery for challenging drugs mainly belonging to Biopharmaceutical Classification System class II (low solubility and high permeability), class III (high solubility and low permeability), and class IV (low solubility and low permeability). Micelles solubilize poorly soluble drugs, shielding them from degradation and macrophage uptake and extending drug action. Their small size enables them to breach ocular barriers, elevating therapeutic impact and bioavailability. This review explores polymeric micelles' potential in ocular drug delivery, covering their introduction, formulation, preparation, characterization, applications, recent progress, and challenges through critical analysis of all possible research communications so far. The review also scrutinizes the transition from lab to clinical use. Polymeric micelles revolutionize ocular drug delivery by surmounting limitations through enhanced solubilization, protection, and sustained release. This comprehensive review highlights their potential to improve ocular drug delivery practices.

Nanozymes, characterized by their nanoscale size and enzyme-like catalytic activities, exhibit diverse therapeutic potentials, including anti-oxidative, anti-inflammatory, anti-microbial, and anti-angiogenic effects. These properties make them highly valuable in nanomedicine, particularly ocular therapy, bypassing the need for systemic delivery. Nanozymes show significant promise in tackling multi-factored ocular diseases, particularly those influenced by oxidation and inflammation, like dry eye disease, and age-related macular degeneration. Their small size, coupled with their ease of modification and integration into soft materials, facilitates the effective penetration of ocular barriers, thereby enabling targeted or prolonged therapy within the eye. This review is dedicated to exploring ocular diseases that are intricately linked to oxidation and inflammation, shedding light on the role of nanozymes in managing these conditions. Additionally, recent studies elucidating advanced applications of nanozymes in ocular therapeutics, along with their integration with soft materials for disease management, are discussed. Finally, this review outlines directions for future investigations aimed at bridging the gap between nanozyme research and clinical applications.

Localized disorders, even though originally confined to a specific body part, can progress into potentially life-threatening systemic disorders if treated inappropriately. Local treatment is often highly challenging due to poor penetration of therapeutic agents from their vehicles into the affected body site. Systemic treatment on the other hand often comes with unspecific side effects. The skin is the largest organ of the body, and conditions such as wounds and bacterial or fungal infections disrupt its natural barrier properties, important for the homeostasis of the human body. Advanced drug delivery systems for treating these conditions could greatly improve the treatment outcome and patient compliance. Other parts of the body that are of interest regarding localized treatment are, for example, the eyes along with mucosal tissues which are present in the vagina and lungs. Rather than focusing on specific diseases or parts of the body, this review provides an overview of the different drug delivery platforms that have been employed for enhanced local treatment. The following systems will be discussed: nanoparticle-based systems, such as nanocrystals, polymeric, lipidic, and inorganic nanoparticles, and nanogels; cyclodextrin inclusion complexes; and several devices like microarray patches, wound dressings, and films.

The existing study focuses on the development, optimization, and evaluation of sorafenib-loaded polymeric nanomicelles for posterior segment delivery in treating retinoblastoma. The formulation involved adjusting various process and product parameters to create effective drug-loaded polymeric nanomicelles. The particle size, PDI, and zeta potential of optimized formulation were found to be 65.52 ± 1.18 nm, 0.14 ± 0.01, and -3.26 ± 0.66 mV, respectively. The entrapment efficiency and drug release were estimated to be 98.84% ± 0.001 and 99.99% in 6 h, respectively. Additionally, the optimized formulation demonstrated acceptable outcomes for solid-state analysis, osmolality, pH, residual solvent, and morphological properties. After 8 h, the ex vivo transcleral permeation and scleral deposition were 629.05 ± 124.11 ng/cm2 and 4.10 ± 0.54 µg, respectively. Y-79 (human retinoblastoma) cell line study using standard drug, test drug, and optimized formulation revealed anticancer potential at all time points (6, 12, 18, and 24 h) with comparable IC50 values. Furthermore, the optimized formulation exhibited no toxicity on the ARPE-19 (human retinal pigmented epithelium) cell line over 24 h. The optimized formulation was non-irritating to the eye (HET-CAM) and remained stable for 6 months. Thus, drug delivery to the posterior eye segment for the treatment of retinoblastoma appears to be possible with the help of established technology.

Eyedrop instillation constitutes the most commonly used ocular drug delivery method that serves for both diagnostic and therapeutic purposes. Ocular disposition and bioavailability of instilled drugs depend on the anatomy and physiology of the ocular surface as well as the physicochemical properties of the active agent. Intraocular bioavailability is positively associated with the amount of drug available onto the ocular surface and the precorneal residence time. Concerns are raised regarding systemic absorption of the instilled drugs intraocularly, percutaneously, via the conjunctiva, through the nasolacrimal system, or through the nasal, oral, and gastrointestinal mucosa. Special considerations exist regarding the anatomical features and the limited pharmacokinetic data on the pediatric population that complicate further the efficacy and systemic toxicity of the instilled medications. Both preclinical and clinical studies propose the reduction of the instilled drop volume, in the form of microdrops, as a means to enhance intraocular bioavailability of topically applied drugs, while minimizing patient discomfort and systemic adverse events. We summarize existing data on the clinical application of microdrops in a wide age range, from preterm infants to elderly adults. Studies regarding microdrops of mydriatics and ocular hypotensives show promising results in optimizing the provided everyday care.

Eye infections such as Acanthamoeba keratitis and bacterial keratitis are serious diseases that could lead to severe, sight-threatening complications. Although moxifloxacin eye drops (0.5 % w/v) is accepted for clinical treatments of these infections, the frequent administration is challenging to achieve the adequate dose due to the limitations of low ocular bioavailability and short retention time. To circumvent these issues, this study developed the extemporaneous moxifloxacin loaded commercial soft hydrogel contact lenses with sustained-release property. The simple soaking method was employed on five common available contact lenses of Acuvue, Biomedics, Maxim, Soflens, and Biotrue, which were immersed in the standard moxifloxacin eye drops solutions. Amongst them, three contact lenses (Acuvue, Biomedics, and Maxim) showed high drug loading of ∼2 mg and adequate controllable drug release for 24 h with Maxim possessing the highest release rate, and maintained the effective drug therapeutic level for at least 12 h. Kinetically, both the moxifloxacin loading and releasing processes followed the Higuchi model, with the diffusion mechanism governing the drug behaviors. Isothermally, the moxifloxacin molecules were adsorbed onto the contact lenses surfaces via physical adsorptions by weak interactions of van der Waals forces, ionic bonding, and hydrophobic interactions. Furthermore, both the eye drops brands (Moximac and Zomoxin), the loading pH (6.7 and 6.0), and the loading time (24 h and 2 h) had no significant effects on the loading and release of moxifloxacin, indicating the system versatility. Conclusively, the extemporaneous moxifloxacin loaded contact lenses, with a duration of action of at least 12 h, could be further explored to become a potential treatment for eye infections.

Poly(amino acids), polypeptides, and their derivatives have demonstrated significant potential as biodegradable biomaterials in the field of drug delivery. As degradable drug carriers, they can effectively load or conjugate drug molecules including small molecule drugs, nucleic acids, peptides, and protein-based drugs, enhancing the stability and targeting of the drugs in vivo. This strategy ultimately facilitates precise drug delivery and controlled release, thereby improving therapeutic efficacy and reducing side effects within the body. This review systematically describes the structural characteristics and preparation methods of poly(amino acids) and polypeptides, summarizes the advantages of poly(amino acids), polypeptides, and their derivatives in drug delivery, and detailedly introduces the latest advancements in this area. The review also discusses current challenges and opportunities associated with poly(amino acids), peptides, and their derivatives, and offers insights into the future directions for these biodegradable materials. This review aims to provide valuable references for scientific research and clinical translation of biodegradable biomaterials based on poly(amino acids) and peptides.

Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation in vitro. Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, in vitro cell barrier models, ex-vivo ocular tissues, and in vivo studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.

Ophthalmic disorders significantly impact global health, affecting millions worldwide. Conventional treatments often face challenges related to poor bioavailability and short residence times on the ocular surface. In recent years, in-situ gels prepared using different natural gums including gellan gum has been investigated as a viable means of improving ocular medication delivery. Gellan gum undergoes ionotropic-gelation in the presence of multivalent cations, making it suitable for ocular formulations. The synthesis and purification of gellan gum involve microbial fermentation processes. Incorporating gellan gum into ophthalmic formulations offers several advantages, including prolonged residence time, enhanced drug retention, and improved bioavailability. Characterisation techniques such as gelling capacity determination, FTIR spectroscopy, TEM, viscosity and rheological studies and ex-vivo or in-vitro release studies are crucial for assessing the structural and functional properties of gellan gum-based in-situ gels. Numerous investigations have exhibited gellan gum's potential in different drug loaded in-situ gels for ophthalmic uses, resulting in extended drug residency on the ocular surface and enhanced therapeutic effects. The current review presents a comprehensive discussion on preparation, characterisation, recent applications and future prospects of gellan gum-based in-situ gels for ocular drug delivery. In addition, it covers molecular structure, synthesis and characterisation of gellan gum.

The administration of corticosteroids is the first-line treatment of the clinical conditions with ocular inflammation. Nonetheless, ocular physiological mechanisms, anatomical barriers and corticosteroid properties prevent it from reaching the target site. Thus, frequent topical administered doses or ocular injections are required, leading to a higher risk of adverse events and poor patient compliance. Designing novel drug delivery systems based on nanotechnological tools is a useful approach to overcome disadvantages associated with the ocular delivery of corticosteroids. Nanoparticle-based drug delivery systems represent an alternative to the current dosage forms for the ocular administration of corticosteroids, since due to their particle size and the properties of their materials, they can increase their solubility, improve ocular permeability, control their release and increase bioavailability after their ocular administration. In this way, lipid and polymer-based nanoparticles have been the main strategies developed, giving rise to novel patent applications to protect these innovative drug delivery systems as a product, its preparation or administration method. Additionally, it should be noted that at least 10 clinical trials are being carried out to evaluate the ocular application of different pharmaceutical formulations based on corticosteroid-loaded nanoparticles. Through a comprehensive and extensive analysis, this review highlights the impact of nanotechnology applications in ocular inflammation therapy with corticosteroids.

Ocular surface chemical injuries often result in permanent visual impairment and necessitate complex, long-term treatments. Immediate and extensive irrigation serves as the first-line intervention, followed by various therapeutic protocols applied throughout different stages of the condition. To optimize outcomes, conventional regimens increasingly incorporate biological agents and surgical techniques. In recent years, nanotechnology has made significant strides, revolutionizing the management of ocular surface chemical injuries by enabling sustained drug release, enhancing treatment efficacy, and minimizing side effects. This review provides a comprehensive analysis of the etiology, epidemiology, classification, and conventional therapies for ocular chemical burns, with a special focus on nanotechnology-based drug delivery systems in managing ocular surface chemical injuries. Twelve categories of nanocarrier platforms are examined, including liposomes, nanoemulsions, nanomicelles, nanowafers, nanostructured lipid carriers, nanoparticles, hydrogels, dendrimers, nanocomplexes, nanofibers, nanozymes, and nanocomposite materials, highlighting their advantages in targeted delivery, biocompatibility, and improved healing efficacy. Additionally, current challenges and limitations in the field are discussed and the future potential of nanotechnology in treating ocular diseases is explored. This review presents the most extensive examination of this topic to date, aiming to link recent advancements with broader therapeutic strategies.

Ozurdex® (Allergan®, AbbVie Company, North Chicago, Illinois, EUA), is composed of 0.7 mg of dexamethasone, fused in a solid biodegradable PLGA polymer, whose degradation occurs naturally in the vitreous cavity, usually in six months after its application.

In this study, we included patients aged ≥ 18 years with one or two eyes who had an indication for Ozurdex® implants. Eyes submitted to Ozurdex® application were evaluated in the first hour after the injection via transpalpebral contact B-scan ocular ultrasonography (Aviso® or Compact Touch®, Quantel®) and non-mydriatic ultra-widefield fundus photography (California®, Optos®) performed sequentially. The exams were executed using similar parameters and techniques, by the same ophthalmologist, after every 45 days, until the end of 180 days. The programed visits were the initial (tagged D0) and sequential (D45, D90, D135, and D180) visits, with a possible variance of seven days, before or after. The ultrasonographic Ozurdex® findings evaluated were: non-quantitative: structure, height, reflectivity, artifact production, location, and movement; and quantitative: length and thickness. Ultra-widefield fundus photography parameters were: Ozurdex® visualization, location, and structure.

The B-scan showed the implant initially, at the D0 visit, as a well-delimited and homogeneously highly reflective linear and continuous structure. On D45, Ozurdex® implants presented with low internal reflectivity and irregularity in the limits. On D90, D135, and D180, reductions in the length and thickness progressively lessened, leading to the final appearance of a small highly reflective clust. Over time, all the implants presented reductions in length and thickness. The mean length at D0 was 7.42 ± 0.39 mm and at the final visit (D180) it was 1.50 ± 0.47 mm. The mean thickness at D0 was 0.77 ± 0.13 mm and at the final visit (D180) it was 0.44 ± 0.18 mm.

Considering implant dimensions, the change in length over time was more evident than the change in thickness. In all the cases where visualization was possible, positive correlations with B-scan findings were found despite changes in patient position. These alterations evidenced in the Ozurdex® implant over time may be related to the degradation of the glucose polymer structure.

Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions. These systems provide advantages over viral vectors, including reduced immunogenicity and enhanced targeting capabilities. This review delves into introduction of common IRDs such as Leber congenital amaurosis, retinitis pigmentosa, Usher syndrome, macular dystrophies, and choroideremia and critically assesses current treatments including neuroprotective agents, cellular therapy, and gene therapy along with their limitations. The focus is on the emerging role of non-viral delivery systems, which promise to address the current limitations of specificity, untoward effects, and immunogenicity in existing gene therapies. Additionally, this review covers recent clinical trial developments in gene therapy for retinal disorders.

Investigating the structural integrity of nanocarriers in vivo is vital for exploring the fate of nanocarriers from ocular surface to the posterior segment of the eye. Most of the published studies adopted the structural integrity ratio of nanocarriers to determine the fate of them, which lacked scientific support. In this study, two methods were used to explore the factors which affected the structural integrity of liposomes. A new method with the standard curve of FRET fluorescence intensity and carbocyanine 7 (Cy7) content was drawn for the first time. Secondly, we used the traditional method of drawing the standard curve of FRET fluorescence efficiency and structural integrity ratios. The results showed that liposomes with particle size about 120 nm, positively charged, polyethyleneglycol5000 (PEG5000) and glycine sarcosine (GS) modified had the highest Cy7 content in rabbit tissues. When the dosage of Cy7 was 25 μg, at 60 min, the content of Cy7 in intact liposomes and the structural integrity ratio of liposomes in sclera was 210.5 ± 14.9 ng and 19.8 ± 5.3 %, respectively. Compared with the structural integrity ratio, the Cy7 content in the intact carrier could better estimate the fate of nanocarriers in vivo scientifically. On this basis, the fate of dual-carrier nanocomposites and the inner cyclodextrin complexes in vivo was investigated. The intact cyclodextrin complexes could reach choroid-retina with the protection of outer liposomes. The structural integrity ratios of liposomes were also studied after crossing human conjunctival epithelial cells (HConEpiC) monolayer, but in vitro cellular experiments could not simulate the real situation in vivo. Finally, the tissue distribution of nanocomposites was studied in rabbit eyes. The concentration of dexamethasone (Dex) in choroid-retina was 158 ± 23 ng/g after 3 h, which exhibited better drug delivery ability compared with our previous study. Overall, the present study provides a new scientific method to estimate the structural integrity in vivo, which is beneficial for the rational design of drug delivery systems with more structural integrity in vivo and higher drug delivery efficiency.

The special structure of eyes and the existence of various physiological barriers make ocular drug delivery one of the most difficult problems in the pharmaceutical field. Considering the problems of patient compliance, local administration remains the preferred method of drug administration in the anterior part of eyes. However, local administration suffers from poor bioavailability, need for frequent administration, and systemic toxicity. Administration in the posterior part of the eye is more difficult, and intravitreal injection is often used. But intravitreal injection faces the problems of poor patient compliance and likely side effects after multiple injections. The development of nanocarrier technology provides an effective way to solve these problems. Among them, liposomes, as the most widely used carrier in clinical application, have the characteristics of amphiphilic nanostructure, easy surface modification, extended release time, good biocompatibility, etc. The liposomes are expected to overcome obstacles and effectively deliver drugs to the target site to improve ocular drug bioavailability. This review summarized the various controllable properties of liposomes for ocular delivery as well as the application and research progress of liposomes in various ocular diseases. In addition, we summarized the physiological barriers and routes of administration contained in eyes, as well as the prospects of liposomes in the treatment of ocular diseases.

The distinct anatomy and physiology of the eye represent it as a specialized organ. The noumenal physiological barriers, whose prominent role is to prevent the entrance of extracellular substances, reduce the bioavailability of medicines taken locally. Nanocarriers offer many advantages, such as site-specific drug delivery, reduced dose-related side effects, more drug loading capacity, etc. Nanoparticles, nano micelles, Nanostructured Lipid Carriers (NLCs), Solid Lipid Nanoparticles (SLNs), liposomes, polymeric nanoparticles, microspheres, microemulsions, etc., have all undergone significant analysis to overcome numerous static and dynamic obstacles.

Among the several methods of delivering drugs, one of the most captivating and demanding is ocular drug delivery (ODD). The intent of developing formulations for an extended period can be partially achieved via thermoresponsive hydrogels. It is feasible to store fluids inside a cross-linked gel system for efficient long-term administration owing to hydrogels, which are hydrophilic polymeric networks with excellent three-dimensional structures and water or biological fluid absorption capacities. Hydrogels can be incorporated into nanocarriers to achieve site-specific action and prolonged release.

Related patents and research reports with various platforms like Science Direct, Springer, PubMed, Google Scholar, Shodhganga, and Patseer were used to gather the data, and a search methodology was availed.

The paper thoroughly summarizes the strategies for incorporating drugs with hydrogel into a nanocarrier to provide sustained release and prolonged therapeutic effects. According to the comprehensive review of literature and patents like (US2015374633A1), (US10980882B2), and (WO2011018800A2), nanocarrier-loaded thermoresponsive hydrogels show promising results.

Due to their propensity to alter state in reaction to temperature changes, thermoresponsive hydrogels can improve medication bioavailability. Intervening nanocarriers loaded hydrogels directly on the targeted site displays local intervention and site-specificity. Thus, the use of nanocarriers in ocular drug delivery is encouraging.

Dry eye disease (DED) is a multifactorial ocular disease, the core mechanism of which is the tear film instability caused by ocular oxidative stress damage and inflammation. Although various pharmaceutical agents are available for DED treatment, their effectiveness is often limited by the eyes' unique biological barriers, and the long-term use of steroid hormones can lead to several adverse effects. This study reported a nano-supramolecular delivery system consisting of a polycyclodextrin (PCD), hyaluronic acid (HA) and the natural compound β-carotene (BC) for the DED treatment. Our findings indicate that the HA/PCD@BC eye drops effectively distribute on the ocular surface, retain BC, and significantly enhance the corneal penetration of BC. The excellent biocompatibility of HA/PCD@BC was demonstrated through viability testing on different cell lines, the Draize eye test, as well as the hematoxylin-eosin staining (H&E) sections of cornea and conjunctiva. Both in vitro oxidative stress assays and in vivo DED model evaluations demonstrated that the HA/PCD@BC delivery system significantly reduced abnormal oxidative stress levels on the ocular surface, inhibited the secretion of inflammatory factors, and increased the secretion of tear film stabilizing mucin. These effects collectively improved pathological changes in eye tissues and minimized damage to the ocular surface. It is of particular importance to note that HA/PCD@BC eye drops showed superior efficacy in comparison to cyclosporine A (CsA), an FDA-approved first-line drug. To sum up, the HA/PCD@BC nanodelivery system provides a natural, safe and effective therapeutic strategy for the treatment of DED and various ocular diseases.

This review paper discusses the key aspects of ocular biopharmaceutics, with emphasis on the crucial role played by ocular compartmental modelling and simulation in deciphering physiological conditions related to various eye diseases. It describes eye's intricate structure and function and the need for precise and targeted drug delivery systems to address prevalent eye conditions. The review categorizes and discusses various formulations employed in ocular drug delivery, delineating their respective advantages and limitations. Additionally, it probes the challenges inherent in diverse routes of drug administration for ocular therapies and provides insights into the complexities of achieving optimal drug concentrations at the target site within the eye. The central theme of this work is the ocular compartmental modelling and simulations. Hence, this works discusses on the nuanced understanding of physiological conditions within the eye, drug distribution, drug release kinetics, and key considerations for ocular compartmental modelling and simulations. By combining information from various sources, this review aims to serve as a comprehensive reference for researchers, clinicians, and pharmaceutical developers. It covers the multifaceted landscape of ocular biopharmaceutics and the transformative impact of modelling and simulation in optimizing ocular drug delivery strategies.

This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. This resulted in an optimum spanlastics (SPLs) formulation with a desirability of 0.919. It had a Span60:Tween80 ratio of 6:1 with a sonication time of 9.5 min. It was evaluated in terms of its EE%, VS, ZP, release behavior in comparison to drug solution in addition to the effect of aging on its characteristics. It had EE% of 87.56, VS of 152.2 nm and ZP of -37.38 Mv. It showed sustained release behavior of PRED in comparison to drug solution with good stability for thirty days. TEM images of the optimized PRED SPLs formulation showed spherical non-aggregated nanovesicles. Then it was loaded into chitosan spongy insert and evaluated in terms of its visual appearance, pH and mucoadhesion properties. It showed good mucoadhesive properties and pH in the safe ocular region. The FTIR, DSC and XRD spectra showed that PRED was successfully entrapped inside the SPLs vesicles. It was then exposed to an in-vivo studies where it was capable of enhancing the anti-inflammatory effect of PRED in a sustained manner with once daily application compared to commercial PRED solution. The spongy insert has the potential to be a promising carrier for the ocular delivery of PRED.

To compare the efficacy of an intracanalicular dexamethasone intracanalicular insert (DII) to a topical prednisolone acetate 1% taper for preventing breakthrough inflammation (iritis or cystoid macular edema [CME]) during the first postoperative month (POM1) after cataract surgery.

Retrospective, nonrandomized comparative interventional study.

Patients received either DII or topical prednisolone acetate 1% eyedrops (control) during POM1. Exclusion criteria included history of iritis, glaucoma, intraoperative posterior capsular rupture or vitreous prolapse, immediate postoperative anterior chamber inflammation requiring treatment, or less than 1 month follow-up postoperatively. Outcomes included development of breakthrough inflammation after >3 days postoperatively necessitating additional antiinflammatory drops, CME, and increased intraocular pressure (IOP) at POM1.

A total of 266 eyes of 174 patients were included in the DII group and 258 eyes of 167 patients in the control group. Demographics, comorbidities, and baseline IOP were comparable between groups. The breakthrough inflammation rate was significantly higher in the DII group compared to control (9.0% vs 3.1%; P < .01); CME rates were similar between groups (4.9% vs 4.3%; P = .75). There were no cases of increased IOP >10 mm Hg at POM1 compared to baseline in either group.

After cataract surgery, DII demonstrated a higher rate of breakthrough inflammation than a standard topical steroid regimen with no significant differences in CME rate or IOP increase; however, overall, the rate of postoperative complications was low. DII can be a safe and effective alternative to topical corticosteroid therapy after cataract surgery.