Search Results (53)

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients. Full article

This study aims to develop and systematically evaluate a new lipid-based formulation of blueberry anthocyanins, which can accelerate the healing effect of the cornea. The study first successfully screened and optimized the formulation and preparation process for blueberry anthocyanin liposomes. Characterization via transmission electron microscopy and dynamic light scattering revealed uniformly distributed, near-spherical liposomes with distinct phospholipid bilayers. Key physicochemical parameters—particle size, zeta potential, encapsulation efficiency, and drug loading capacity—all met formulation standards. In vivo pharmacodynamic experiments demonstrated that topical administration of blueberry anthocyanin liposomes significantly accelerated the repair process and effectively mitigated depressional damage to the corneal epithelium in a New Zealand white rabbit corneal injury model induced by 10.6 μm mid-infrared CO₂ laser. In summary, the blueberry anthocyanin liposomes successfully prepared in this study exhibit excellent performance, effectively enhancing drug exposure levels in vivo and promoting corneal repair. This provides reliable experimental evidence for the development of plant natural active ingredients in ophthalmic treatments. Full article

Ocular diseases pose significant therapeutic challenges due to the eye’s intricate anatomy and efficient physiological clearance mechanisms, which result in the rapid elimination of topically administered drugs and an overall bioavailability of less than 5%. Anterior segment disorders—including keratitis, glaucoma, and dry eye syndrome—account for the majority of ophthalmic conditions and are primarily managed with pharmacological agents. However, due to extremely low drug bioavailability and poor patient compliance, their therapeutic outcomes often result in a decreased disease control rate or require early surgical interventions. Nebulized drug delivery, particularly employing advanced vibrating mesh technology, has emerged as a promising strategy to overcome these limitations. By converting liquid formulations into a uniform aerosol of micron-sized (1–10 μm) droplets, this approach achieves extensive and consistent coverage of the ocular surface, increases the absorption contact area, prolongs drug residence time, and ultimately enhances drug bioavailability. Preliminary clinical evidence indicates that nebulized therapies outperform traditional eye drops by achieving higher drug concentrations in the aqueous humor and demonstrating superior pharmacodynamic profiles and patient tolerability—particularly in conditions such as dry eye syndrome and glaucoma. This review presents a comprehensive overview of the mechanistic principles, technological advancements, and translational applications of nebulization-based ocular drug delivery systems. We place special emphasis on the integration of next-generation platforms that incorporate microelectromechanical systems (MEMS) and intelligent sensing technologies, enabling precision medicine approaches tailored to individual ocular pathophysiological characteristics. By bridging biomedical engineering and clinical ophthalmology, these innovations not only optimize existing therapeutic regimens but also pave the way for non-invasive delivery of complex biologics and gene therapies—potentially reshaping the landscape of anterior segment drug delivery. Full article

Hyaluronic acid (HA)–based nanocapsules containing plant-derived bioactives are promising formulations for dermatological applications. In this study, nanocapsules containing extracts of Arnica montana, Calendula officinalis and Aesculus hippocastanum were synthesized and their structural and functional properties were characterized. Scanning electron microscopy confirmed the formation of spherical nanostructures with uniform morphology, while rheological analyses demonstrated stable viscoelastic behavior suitable for topical application. Their antimicrobial potential was assessed on microorganisms isolated from multiple regions of healthy human skin and opportunistic pathogens. A diverse panel of approx. 100 bacterial and fungal isolates was identified using MALDI-TOF MS. The antimicrobial activity of formulations was compared with commonly used disinfectants: H₂O₂, octenidine, isopropanol and topical ophthalmic antiseptic. Arnica-based formulations showed the strongest inhibitory effect against both Gram-positive and Gram-negative bacteria, whereas chestnut extract demonstrated selective activity against Candida spp. Calendula-based formulations exhibited limited antimicrobial activity. These findings demonstrate that plant-extract-loaded HA nanocapsules exhibit selective antimicrobial properties dependent on extract type and microbial group, supporting their potential as multifunctional components of future dermatological formulations. Full article

Corneal fibrosis remains a major cause of visual morbidity, with transforming growth factor-β (TGF-β) signaling playing a central role in this process. Losartan, an angiotensin II type 1 receptor blocker widely used systemically for cardiovascular indications, has recently attracted interest in ophthalmology due to its antifibrotic properties through indirect inhibition of TGF-β signaling. In recent years, increasing experimental and early clinical evidence has suggested that topical ophthalmic formulations of losartan may attenuate corneal fibrosis following diverse injuries such as descemetorhexis, alkali burns, and photorefractive keratectomy-related injury. Topical losartan represents a promising, non-cytotoxic antifibrotic strategy in ophthalmology, although human evidence is limited and further randomized controlled clinical trials are required to define its clinical efficacy, optimal indications, timing, posology, formulations, and long-term safety. This review summarizes the biological rationale for the use of topical losartan in ophthalmology, including its molecular mechanisms of action, pharmacologic considerations, and safety profile. We critically review preclinical studies in corneal models, as well as emerging clinical applications. Full article

Background: The use of preservative agents in eye drop solutions may worsen symptoms of ocular surface disease, which is a highly prevalent syndrome worldwide. Preservatives are often used in pharmacotherapy of glaucoma, another disease concerning tens of millions of people around the globe. These numbers are predicted by the World Health Organization and are predicted to increase with time due to constant aging of populations. Methods: PubMed and Scopus databases were searched for articles investigating the topic of ocular surface disease in relation with glaucoma pharmacotherapy, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The aim of this review is to summarize the effect of various solvents used in drug formulations and ways to quantify their impact on the ocular surface. Discussion and Conclusions: Topical ophthalmic preservative-free formulations are better tolerated and less burdensome for all patients. They should be considered especially for glaucoma patients, who are expected to take medications for years, up to decades or a lifetime in many cases. Due to the chronicity of dry eye disease and the lack of reliable ways for lacrimal and meibomian gland renewal, primary prophylaxis is of uttermost importance. Unfortunately, despite the development of many measuring devices, the standardization of diagnostic methods poses a challenge due to high variability of results which are influenced by a myriad of factors—local, internal, and external. Full article

Background: Fungal keratitis is a serious ophthalmic problem due to low antifungal medication penetration and bioavailability at the ocular surface, necessitating novel delivery strategies for successful therapeutic outcomes. This study created amphotericin B-loaded silk fibroin nanoparticles (AmB-SFNs) as a targeted drug delivery platform for long-term ocular antifungal therapy. Methods: Silk fibroin-chitosan nanoparticles were produced using a precipitation technique, with chitosan coating for mucoadhesion and polyethylene glycol-400 surface stability. Clinical fungal isolates from keratitis patients were identified as species by morphological and molecular analysis, followed by in vitro antifungal susceptibility testing. Results: The optimized formulation produced spherical AmB-SFNs with an average diameter of 220 nm, a positive zeta potential of +34 mV, and a maximum amphotericin B entrapment effectiveness of 76%. Molecular identification confirmed that all five clinical isolates were Fusarium solani. AmB-SFNs showed strong antifungal activity against all tested isolates, with a minimum inhibitory dose of 50 μg/mL (0.25% w/v). Conclusions: The developed nanoparticulate system has optimal characteristics for enhanced corneal drug delivery, such as appropriate particle size for tissue penetration and mucoadhesive properties for prolonged ocular residence time, suggesting that this nanoparticulate system warrants further investigation in vivo to evaluate its potential for clinical translation in treating Fusarium keratitis and as a platform for topical ophthalmic therapies. Full article

Background/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient’s lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg/kg, which is substantially lower than the 20 mg/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h·ng/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2–32 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5–10 ng/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration. Full article

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. Full article

Cyclodextrins (CDs) have revolutionized the pharmaceutical industry with their ability to enhance the stability, solubility, and bioavailability of a wide range of active substances. These cyclic oligosaccharides, with a unique hydrophilic exterior and hydrophobic cavity, form inclusion complexes with poorly soluble drugs, improving their pharmacokinetic profiles and therapeutic efficacy. This review explores the multifaceted roles of cyclodextrins in pharmaceutical formulations, ranging from oral, ophthalmic, parenteral, and topical applications to their emerging use in targeted therapies, gene delivery, and treatment of neurodegenerative, cardiovascular, and infectious diseases. Cyclodextrins not only improve drug solubility and controlled release but also reduce toxicity and side effects, leading to safer and more effective treatments. Recent advancements, such as cyclodextrin-based nanoparticles, offer promising pathways for cancer therapy, chronic disease management, and personalized medicine. As research continues, cyclodextrins remain at the forefront of innovation in drug delivery systems, ensuring better patient outcomes and expanding the possibilities of modern therapeutics. Full article

Doxycycline (Dxy), a broad-spectrum antibiotic with anti-inflammatory effects, is commonly used in ophthalmology but is unstable as a topical eyedrop, degrading quickly into inactive forms and requiring frequent application. To address this, gelatin nanoparticles (GNPs) loaded with Dxy (DNPs) were developed as a stable ophthalmic nanomedicine for enhancing corneal wound healing by inhibiting matrix metalloproteinases (MMPs). In this study, female Sprague–Dawley rats underwent lamellar keratectomy, and various Dxy formulations—oral, conventional eyedrops, and DNP-containing eyedrops—were evaluated for corneal wound repair. Clinical assessments included fluorescein staining, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD-OCT) imaging, histopathology, and immunohistochemistry for MMP-2, MMP-9, and α-SMA. The DNP group (0.01% Dxy in DNPs, applied twice daily) demonstrated faster corneal thickness recovery and epithelial healing on days 7 and 14 compared to 0.1% Dxy eyedrop treatments applied twice or four times daily. DNP-treated eyes also showed reduced angiogenesis intensity and lower MMP-2 and MMP-9 immunoreactive scores, with enhanced stromal recovery and reduced neovascularization. These results highlight DNPs’ potential as a superior treatment for corneal wounds, providing effective healing with less frequent dosing and lower drug concentrations. This study supports DNPs’ potential for clinical application as a stable and efficient therapeutic agent in ophthalmology. Full article

The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use. Applying a composite in situ thermoresponsive hydrogel formulation embedded with polymer nanoparticles is a potent strategy to overcome all the identified drawbacks. In the present work we prepared uniform spherical nanoparticles (296.4 ± 3.1 nm) efficiently loaded with curcumin (EE% 82.5 ± 2.3%) based on the biocompatible and biodegradable poly-(lactic-co-glycolic acid). They were thoroughly physicochemically characterized in terms of FTIR, SEM, TGA, and DLS, in vitro release following Fickian diffusion (45.62 ± 2.37%), and stability over 6 months. Their lack of cytotoxicity was demonstrated in vitro on HaCaT cell lines, and the potential for antioxidant protection was also outlined, starting from concentrations as low as 0.1 µM and reaching 41% protection at 5 µM. An in situ thermoresponsive hydrogel (17% w/v poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 ± 0.36 °C), gelling time (8.99 ± 0.28 s) upon tears dilution, and gel erosion (90.75 ± 4.06%). Upon curcumin-loaded nanoparticle embedding, the in situ hydrogels demonstrated appropriate pseudoplastic behavior and viscosity at 35 °C (2129 ± 24 Pa∙s), 6-fold increase in the permeation, and prolonged release over 6 h. Full article

The development of generic ophthalmic drug products with complex formulations is challenging due to the complexity of the ocular system and a lack of sensitive testing to evaluate the interplay of its physiology with ophthalmic drugs. New methods are needed to facilitate the development of ophthalmic generic drug products. Ocular physiologically based pharmacokinetic (O-PBPK) models can provide insight into drug partitioning in eye tissues that are usually not accessible and/or are challenging to sample in humans. This study aims to demonstrate the utility of an ocular PBPK model to predict human exposure following the administration of ophthalmic suspension. Besifloxacin (Bes) suspension is presented as a case study. The O-PBPK model for Bes ophthalmic suspension (Besivance^® 0.6%) accounts for nasolacrimal drainage, suspended particle dissolution in the tears, ocular absorption, and distribution in the rabbit eye. A topical controlled release formulation was used to integrate the effect of Durasite^® on Bes ocular retention. The model was subsequently used to predict Bes exposure after its topical administration in humans. Drug-specific parameters were used as validated for rabbits. The physiological parameters were adjusted to match human ocular physiology. Simulated human ocular pharmacokinetic profiles were compared with the observed ocular tissue concentration data to assess the OCAT models’ ability to predict human ocular exposure. The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful. Full article

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. Full article

Purpose: Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia. Methods: The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed. Results: 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by −1.1 ± 0.27 points in the treatment and −0.6 ± 0.79 points in the placebo group (p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred. Conclusions: A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia. Full article