Search Results (418)

Glaucoma is an ocular disease caused by the improper management of elevated intraocular pressure (IOP). IOP-lowering via topical administration is the first choice to prevent further progression. However, patients may forget to administer their medication, compromising IOP control. To address this problem, a prolonged active pharmaceutical ingredient (API) release system is proposed. A new prodrug (latanoprost acid–brimonidine conjugate, LBJ) was designed and expected to achieve potential long-lasting release of APIs. LBJ was synthesized by two methods. First, Steglich esterification without protecting the hydroxyl group led to a yield of 34.24%. However, the integral ratio between LPA and BM obtained from NMR was 1.25:1, indicating a potential side product resulting from further coupling through the unprotected hydroxyl group in LBJ. As an alternative route, Steglich esterification with a protecting agent, tert-butyldimethylchlorosilane (TBDMSCl), resulted in a yield of 39.35%, and the integral ratio between LPA and BM obtained from NMR was 1:1. The hydrolysis time of LBJ was investigated and compared with that of latanoprost (LP). In the presence of esterase (0.4 U/mL), the hydrolysis times of LP and LBJ were 4 h and 28 days, respectively. The prolonged hydrolysis time results in sustained APIs release, which is beneficial for the development of a sustained drug release system. Full article

Background: Ocular drug delivery is hindered by the eye’s complex anatomy and multiple physiological barriers. Because of their biocompatibility, biodegradability, and capacity to prolong drug retention, hydrogels have emerged as promising platforms for ocular drug delivery. This study provides a bibliometric and visual analysis of research on hydrogel-based ocular drug delivery from 1991 to 25 August 2025. Methods: Publications were retrieved from the Web of Science Core Collection and screened for relevance. CiteSpace, VOSviewer, and the Bibliometrix R package were used to analyze annual publication trends, contributions and collaborations among countries, institutions, and authors, core journals, and evolving research themes. Results: A total of 1354 publications (991 articles and 363 reviews) were included. Annual output increased markedly after 2007–2008, reflecting rapid growth in this field. China and the USA were the leading contributors, and the University of Florida was the most productive institution. Keyword co-occurrence, clustering, and burst analyses identified in situ hydrogels, tissue engineering applications, and anti-VEGF delivery as major research hotspots. Conclusions: This study maps the growth and diversification of hydrogel-based ocular drug delivery research, revealing a shift toward disease- and segment-specific applications, with controlled-release, stimuli-responsive systems, injectable hydrogels, and anti-VEGF as emerging research priorities. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating frequent administration. In this study, we developed an eyelid-applied drug delivery system (DDS) based on troxipide (TRO) nanoparticle formulation (TRO-NP@EG) to achieve sustained ocular surface delivery. Methods: TRO nanosuspensions were prepared by wet bead milling and incorporated into a Carbopol-based gel. Particle size, dispersion stability, and uniformity were evaluated, and in vitro drug release studies was compared with that of TRO-MP@EG. In vivo drug transfer into tear fluid was assessed in rabbits following eyelid application, and therapeutic efficacy was evaluated in an N-acetylcysteine-induced dry eye model. Results: TRO nanosuspensions had a mean particle size of approximately 118 nm. TRO-NP@EG exhibited superior dispersion stability and uniformity and achieved 2.5-fold higher drug release than TRO-MP@EG, while the nanoparticles remained in solid form. In vivo studies in rabbits, TRO-NP@EG significantly enhanced drug transfer into tear fluid, primarily via the meibum pathway. Furthermore, TRO-NP@EG significantly improved mucin levels, tear secretion, and tear film stability compared with TRO-MP@EG in an N-acetylcysteine-induced dry eye model. Conclusions: These findings suggest that eyelid application of nanoparticle-based formulations enables efficient and sustained drug delivery to the ocular surface via the meibomian glands. Therefore, TRO-NP@EG represents a promising therapeutic strategy for DED, providing enhanced efficacy and a novel route of administration for ophthalmic DDSs. Full article

Eye drops remain the principal topical treatment for ocular infections, yet rapid precorneal clearance, variable dose delivery and limited tissue penetration can restrict local drug availability and necessitate frequent administration. Conjunctival inserts have long been investigated as a means of extending ocular residence and thin film inserts offer a more adaptable solid dosage form that may provide a defined drug-containing unit, prolonged local exposure and hydration-dependent dissolution or transformation within the conjunctival sac. Clinical translation remains limited by substantial variability in formulation design, manufacturing control and performance testing. This review critically evaluates the manufacture and characterisation of ocular anti-infective thin film inserts, with the aim of identifying the principal factors that determine reproducibility, interpretability and progression beyond formulation feasibility. Film architecture, polymer selection and drug-loading strategy are considered in relation to the physicochemical characteristics of the active pharmaceutical ingredient and the intended behaviour of the finished insert. Solvent casting remains the most extensively investigated manufacturing approach, while extrusion, electrospinning and additive manufacturing broaden the available processing options. Across these methods, incomplete specification of material and process variables frequently restricts comparison and reproducibility. Testing procedures are similarly heterogeneous and often assess individual attributes without establishing how the finished insert performs under conditions relevant to conjunctival administration. Particular limitations concern dosage-unit uniformity, hydration and matrix transformation, drug-release models and the interpretation of antimicrobial activity. Progression towards clinically relevant products will require indication-led development in which manufacturing control, pharmaceutical quality, ocular compatibility and biorelevant performance evaluation are considered as connected elements. This approach may provide a stronger basis for determining whether the potential advantages of ocular anti-infective thin film inserts can be translated into reproducible and clinically useful dosage forms. Full article

Eosinophils are tissue-adapted granulocytes with important roles in host defense, immune regulation, barrier responses, and inflammatory disease. Beyond classical degranulation, activated eosinophils can release eosinophil extracellular traps (EETs), extracellular DNA and protein structures that arise through cytolytic nuclear EETosis or rapid mitochondrial DNA (mtDNA) release. These traps may contribute to host protection by immobilizing pathogens and concentrating eosinophil granule proteins at sites of mucosal or tissue inflammation. However, when EET formation is excessive, persistent, or insufficiently cleared, the same structures may promote epithelial injury, mucus viscosity, thromboinflammation, tissue remodeling, fibrosis, and chronic eosinophilic inflammation. This review summarizes the cellular mechanisms, structural organization, inducing stimuli, and disease relevance of EETs. Particular attention is given to infectious settings, eosinophilic airway and middle-ear disease, systemic vasculitic and hypereosinophilic disorders, inflammatory skin and ocular diseases, eosinophilic gastrointestinal disease, and cancer. Current evidence indicates that EETs should be interpreted as context-dependent eosinophil effector structures with dual biological potential. Although their mechanistic relevance is increasingly recognized, further histological, functional, and clinical validation is needed before EETs can be established as reliable biomarkers or therapeutic targets. Full article

Nanoparticle-laden contact lenses (CLs) represent a promising strategy for ocular drug delivery. Nanocarriers built from hyaluronic acid and chitosan offer a biomimetic alternative to synthetic polymers, by combining the lubricating property of hyaluronic acid with the mucoadhesive property of chitosan. However, achieving sustained drug release without compromising lens properties remains challenging, and the influence of lens material and replacement modality is unclear. This study evaluated methotrexate (MTX)-loaded chitosan/hyaluronic acid (CS/HA) nanoparticles incorporated into silicone hydrogel CLs with different replacement modalities, assessing their effect on drug release kinetics. Daily replacement lenses (Senofilcon A and Delefilcon A) released 26 ± 4% and 33 ± 5% of MTX after 24 h, respectively. The monthly lens Lehfilcon A showed slower diffusion-controlled release, with only 15 ± 2% released at 24 h and a 64 ± 3% cumulative release after 31 days (p < 0.01). Nanoparticle incorporation improved drug retention and reduced initial drug loss compared with lenses loaded with only MTX. Monthly lenses demonstrated sustained delivery potential, supporting prolonged ocular therapy, while daily lenses may be better suited for short-term treatment. These findings reinforce the value of bioinspired nanocarriers, mimicking natural retention mechanisms of the ocular surface, for next-generation therapeutic CLs. Full article

Nanomedicine-based liposomal delivery systems are gaining increasing attention as advanced therapeutic platforms for managing ocular infections associated with antimicrobial resistance (AMR) and biofilm formation. The primary objective of this review is to critically evaluate the potential of liposomal drug delivery systems for improving the treatment of antimicrobial-resistant and biofilm-associated ocular infections by integrating current knowledge on antimicrobial resistance mechanisms, biofilm-targeted therapeutic strategies, and advances in liposomal formulations, while also identifying the major limitations, translational challenges, and knowledge gaps in this rapidly evolving field. Traditional ocular antimicrobial treatments are frequently limited by poor drug penetration, short precorneal residence time, low bioavailability, systemic side effects, and inadequate activity against resistant microorganisms and biofilm-embedded pathogens. This review provides a comprehensive overview of different liposomal systems, including conventional, cationic, polyethylene glycol (PEG)-modified, deformable, and stimulus-responsive liposomes, and discusses their advantages in ophthalmic drug delivery, such as enhanced corneal permeation, prolonged drug retention, controlled release, improved biocompatibility, and reduced ocular toxicity. The review further examines the mechanisms through which liposomes help overcome AMR, including improved epithelial transport, membrane disruption, intracellular drug delivery, efflux pump evasion, and enhanced antimicrobial efficacy. In addition, liposomal approaches targeting ocular biofilms are explored, focusing on improved biofilm penetration and the delivery of anti-biofilm agents such as antibiotics, enzymes, quorum-sensing inhibitors, and antimicrobial peptides. Current evidence from in vitro and in vivo ocular infection models is summarized together with disease-specific applications in keratitis, endophthalmitis, and contact lens-related infections. The article also compares liposomes with other ocular nanocarriers and addresses important considerations related to safety, stability, sterilization, large-scale production, and regulatory translation. In addition to highlighting recent advances, this review critically discusses the current limitations of liposomal formulations, the major barriers to clinical translation, and the key knowledge gaps that should be addressed to facilitate the future development and successful clinical application of these systems. Finally, emerging directions including ligand-targeted and stimulus-responsive liposomes, AI-driven formulation development, personalized nanotherapy, and gene therapy combinations are discussed as promising future strategies for combating resistant ocular infections. Full article

Objective: This study aimed to enhance wound healing by developing a delivery platform that combines camel milk-derived extracellular vesicles (CM-EVs) with a thermosensitive chitosan/Poloxamer 407 hydrogel (CM-EVs–Gel), addressing the challenges of instability, poor skin penetration, and burst release associated with EVs. Methods: CM-EVs were isolated and analyzed for size, markers, and protein content. A thermosensitive hydrogel was created and infused with CM-EVs. Its gelation, injectability, and release kinetics (using the Higuchi model) were tested. Safety was evaluated through ocular irritation and 28-day skin toxicity in rabbits. Wound healing effectiveness was tested in rats with full-thickness wounds, comparing CM-EVs–Gel, a blank hydrogel, and untreated controls. Results: CM-EVs had an average size of 108.5 nm and expressed CD63, CD81, and Alix. The hydrogel solidified at 37 °C within 10 min and followed the Higuchi model for diffusion-controlled release (R² = 0.974), releasing 81.7% of EVs over 48 h without toxicity. In rats, CM-EVs–Gel achieved 76.31% wound closure by day 6 and 94.7% by day 15, outperforming blank hydrogel (48.77% and 82.1%) and untreated controls (43.14% and 72.3%) (p < 0.01). Histology showed improved re-epithelialization, collagen deposition, and angiogenesis. Conclusions: This study shows that integrating biogenic particle engineering with optimized hydrogel systems allows for controlled release, safety, and enhanced wound healing. Despite missing free EV controls, full rheological data, and mechanistic insights, it highlights comprehensive delivery strategies from particle design to system performance, aligning with the Special Issue’s focus. Full article

Background: Tuberculosis (TB) remains a major global health problem, particularly in children, who are at higher risk of extrapulmonary and disseminated disease. Ocular tuberculosis is a rare manifestation and often presents with nonspecific signs, leading to delayed diagnosis. Case Presentation: We report the case of a five-year-old previously healthy boy presenting with a two-month history of persistent fever. Initial investigations revealed a positive tuberculin skin test and interferon gamma release assay, with chest CT findings suggestive of miliary TB. Despite negative microbiological tests, antitubercular therapy was initiated. Ophthalmologic evaluation showed preserved visual acuity, bilateral mild papilledema, and multifocal chorioretinitis. Neuroimaging confirmed central nervous system involvement with disseminated tubercular lesions. Fundus examination revealed grade 1 papilledema and chorioretinal lesions. Ocular ultrasound demonstrated an increased optic nerve sheath diameter consistent with intracranial hypertension. Brain MRI showed intra-axial tubercular dissemination. Extensive infectious and immunological testing excluded alternative diagnoses. The patient received prolonged multidrug antitubercular therapy, including isoniazid, rifampicin, ethambutol, pyrazinamide, amikacin, levofloxacin, and corticosteroids. Treatment was continued for a total of 15 months. Ocular findings regressed within two months, and complete systemic resolution was achieved by 21 months. At a five-year follow-up, the patient remained in good health with normal neurodevelopment and no disease recurrence. Conclusions: This case underscores the importance of considering ocular TB in children with prolonged fever and subtle ocular findings. Early ophthalmologic evaluation and prompt initiation of antitubercular therapy are essential to prevent severe complications and ensure favorable outcomes. Full article

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001–2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA^® (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30–60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms. Full article

Background/Objectives: Despite available treatment options, glaucoma continues to be a leading cause of irreversible blindness. Current medications have multiple limitations, including rapid drainage, ocular irritation, requirement for multiple daily dosings, and systemic side effects. The current study was designed to engineer and characterize a pregabalin-containing enhanced delivery formulation (PRG-EDF) to directly address these inadequacies. Methods: PRG-EDF eye drops were prepared using ingredients that are either U.S. Food and Drug Administration (FDA)-approved for ophthalmic use or have established safety profiles. The formulation was characterized using multiple evaluations, including pH, zetasizer analyses, viscosity, in vitro drug release, transcorneal permeability, determination of dose concentration and volume, systemic exposure, and potential for tachyphylaxis. Efficacy was evaluated using both Dutch belted rabbits and baboons. Results: PRG-EDF provides extended release for up to 24 h. Ex vivo data reveal that PRG-EDF does not alter the inherent high PRG corneal permeability. An intraocular pressure (IOP) study using DB rabbits demonstrates that 40 µL of PRG-EDF, 0.6%, is the optimum dose of our formulation. Comparison of the efficacy of PRG-EDF with commercial products demonstrated its superiority in overall IOP-lowering efficacy. An extended in vivo assessment demonstrated that the potency of PRG-EDF reached maximum IOP-lowering amplitude after 4 weeks of daily dosing. Moreover, an in vivo bioadhesion assay demonstrated that EDF remained on the ocular surface for up to 24 h. Impressively, PRG-EDF is as effective in baboons as in rabbits. Conclusions: We have successfully engineered a highly promising once-daily glaucoma medication with superior efficacy, as illustrated by higher IOP-lowering ability and prolonged duration of action. Full article

Vernal keratoconjunctivitis (VKC) is a chronic condition that causes remodeling of the cornea and conjunctiva through recurring episodes of allergic inflammation of the ocular surface. This can lead to corneal scarring, keratoconus, and chronic conjunctival papillae. However, the details of the immunopathological processes behind these remodeling changes are not completely understood. Despite involving IgE-modulated mechanisms, about half of patients with VKC test negative on systemic allergy tests. This calls for the need to understand the common and novel inflammatory mediators involved in the pathogenesis of VKC development and severity levels. Eye rubbing stimulates the release of inflammatory cytokines TNF-alpha, IL-4, IL-5, and IL-13 and remodeling enzymes MMP-1, MMP-3, MMP-9, and MMP-10, which drive a dysregulated cycle of stromal tissue remodeling that leads to progressive ectasia. Eosinophilic activity is driven by CCL11 and ICAM-1 and eye rubbing, which leads to degranulation and the release of EMBP, ECP, and MMP-9. These inflammatory mediators drive the remodeling changes that lead to corneal scarring and ectasia. The purpose of this comprehensive review paper is to shed light on common and novel immunological mediators that help us further understand VKC and eventually lead to the discovery of more effective and targeted treatment options. Full article

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Mucoadhesive drug delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of pharmaceuticals by improving drug residence time, bioavailability, and site-specific targeting. Among various materials investigated, biopolysaccharides have gained significant attention due to their biocompatibility, biodegradability, non-toxicity, and inherent mucoadhesive properties. Natural polymers such as chitosan, alginate, pectin, hyaluronic acid, and cellulose derivatives exhibit strong interactions with mucosal surfaces through hydrogen bonding, electrostatic interactions, and polymer chain entanglement. These properties enable prolonged drug retention at mucosal sites, controlled drug release, and enhanced permeation across biological barriers. Mucoadhesive biopolysaccharides have been explored for diverse routes of administration, including oral, buccal, nasal, ocular, vaginal, and pulmonary delivery. Furthermore, chemical modification and nanostructuring of these polymers have expanded their functionality, enabling targeted delivery of small molecules, proteins, peptides, and nucleic acids. This review highlights the mechanisms of mucoadhesion, key biopolysaccharides used in drug delivery, formulation approaches, and recent advances in their application as versatile platforms for novel therapeutic delivery systems. The continued development of mucoadhesive biopolysaccharide-based carriers holds substantial potential for improving treatment outcomes and patient compliance. Full article

Electroretinography (ERG) is a non-invasive technique used to assess retinal function via electrical responses to light stimuli. We established baseline ERG parameters and a standardized recording protocol for collared scops owls (Otus lettia). Twelve eyes of six owls were evaluated. In addition to the pre-release assessment, ocular reflex tests and basic ophthalmic examinations were performed before the induction of anesthesia. Routine radiographic and hematological examinations were performed under general anesthesia, followed by ERG recordings. Under scotopic –20 dB conditions, the a-wave amplitude was 1.78 ± 0.53 μV (implicit time: 37.83 ± 5.52 ms), and the b-wave was 41.59 ± 10.71 μV (100.88 ± 10.9 ms). For scotopic 0 dB mixed responses, the a-wave amplitude was 27.98 ± 5.9 μV (27.64 ± 2.71 ms), and that of the b-wave was 175.51 ± 13.82 μV (97.02 ± 7.01 ms). Under photopic conditions, the a-wave and b-wave amplitudes were 2.88 ± 2.06 μV (28.67 ± 2.77 ms) and 25.53 ± 10.61 μV (77.78 ± 16.18 ms). To the best of our knowledge, this is the first study to establish species-specific baseline ERG parameters for collared scops owls. These findings provide a valuable tool for assessing retinal function in raptors and may serve as a baseline framework for ERG evaluation in other avian species. Full article