Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

ACS Nano, Journal Year: 2023, Volume and Issue: 17(24), P. 25118 - 25135

Published: Dec. 5, 2023

Dry eye (DE) disease, which is primarily linked to aqueous deficiency, an escalating health issue worldwide, mainly due the widespread use of electronic devices. The major obstacles in DE pharmacotherapy include insufficient therapeutic efficacy and low ocular bioavailability. This study presents development a ceria-based nanosystem carry gabapentin (GBT), aiming offer comprehensive relief from symptoms. We prepared multifunctional nanoceria capped with thiolated gelatin followed by cross-linking glutaraldehyde, yielding nanocarrier desirable biocompatibility antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, neuronal protective activities. Specifically, highly abundant thiol groups on increased cellular uptake 2.3-fold its mucin-binding efficiency 10-fold, thereby extending retention amplifying activity. Moderate not only enhanced bioavailability but also provided slow, degradation-controlled release GBT promote lacrimal stimulation restore tear film. In rabbit model DE, topical administration our GBT/nanoceria nanoformulation resulted alleviation symptoms, including repairing corneal epithelial damage, preserving nerve density, stimulating secretion, demonstrating superior performance comparison free drug. These results underscore safety potential this innovative for pharmacotherapy.

Language: Английский

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Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(4), P. 1094 - 1094

Published: March 29, 2023

Posterior segment eye diseases present a challenge in treatment due to the complex structures that serve as robust static and dynamic barriers, limiting penetration, residence time, bioavailability of topical intraocular medications. This hinders effective requires frequent dosing, such regular use drops or visits ophthalmologist for intravitreal injections, manage disease. Moreover, drugs must be biodegradable minimize toxicity adverse reactions, well small enough not affect visual axis. The development nano-based drug delivery systems (DDSs) can solution these challenges. First, they stay ocular tissues longer periods reducing frequency administration. Second, pass through offering higher targeted are otherwise inaccessible. Third, made up polymers nanosized. Hence, therapeutic innovations nanosized DDS have been widely explored ophthalmic applications. In this review, we will concise overview DDSs utilized diseases. We then examine current challenges faced management posterior explore how various types nanocarriers enhance our arsenal. A literature review pre-clinical clinical studies published between 2017 2023 was conducted. Through advances materials, combined with better understanding pharmacology, rapidly evolved, showing great promise overcome currently encountered by clinicians.

Language: Английский

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Advances in Sjögren’s Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 80 - 80

Published: Jan. 8, 2024

Sjögren’s syndrome dry eye (SSDE) is a subset of marked by symptoms that distinct from non-Sjögren’s (NSSDE). As SSDE can lead to severe complications, its early detection imperative. However, the differentiation between and NSSDE remains challenging due overlapping clinical manifestations. This review endeavors give concise overview classification, pathophysiology, features presentation, ocular systemic diagnosis, management SSDE. Despite advancements, limitations in current diagnostic methods underscore need for novel modalities. Thus, examines various biomarkers utilized identification, encompassing serum, salivary, tear analyses. Recent advancements proteomic research exosomal offer promising potential. Through comprehensive literature spanning 2016 2023, we highlight molecular insights advanced modalities have potential enhance our understanding diagnosis

Language: Английский

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A Review of the Impact of Sjögren’s Syndrome and/or the Presence of Anti-Ro/SS-A Antibodies on Therapeutic Strategies for Rheumatoid Arthritis

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 568 - 568

Published: Jan. 17, 2025

Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren’s syndrome (SS), another rheumatic caused lymphocytic infiltration exocrine glands, dry eye mouth being two most symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker SS, are positive in patients at certain rate. The coexistence SS and/or positivity for anti-Ro/SS-A antibodies influences activity effectiveness classes disease-modifying antirheumatic drugs (DMARDs). Furthermore, RA, DMARDs, including methotrexate, associated onset lymphoproliferative disorders (LPD). In contrast, biological such as tocilizumab rituximab, plausible options without risk LPD relapse. Considering results studies introduced this article, could be considered phenotype different from isolated perspective refractoriness to DMARD therapy risk. Hence, rheumatologists should observe caution when choosing DMARDs. Further needed establish appropriate treatment presence antibodies.

Language: Английский

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Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 28, 2025

Background Sjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component tears, SjD-associated dacryoadenitis (AD) may thus alter tear autoantibody composition. Methods presence tertiary lymphoid structures (TLS) in from two murine models AD, male non-obese diabetic (NOD) insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG IgA reactivity serum tears these probed three studies against a panel 80-120 autoantigens microarrays relative to healthy BALB/c mice. Sources Ig investigated scRNA-Seq (GSE132420). Data analyzed R package Limma Seurat. Results Analysis immunofluorescence sections both SjD showed TLS. Only one was significantly elevated across all studies. Three autoantibodies but not Conversely, six thirteen (6 sharing same autoantigen) models. Igha Ighg2b expressing cells identified plasma cell cluster NOD.H2b LG. Conclusion NOD NOR mice with AD have distinct profiles serum. Tear isotype greater diversity than autoantibodies. TLS observed are likely source

Language: Английский

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A first-in-human, prospective pilot trial of umbilical cord-derived mesenchymal stem cell eye drops therapy for patients with refractory non-Sjögren's and Sjögren's syndrome dry eye disease

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 23, 2025

Patients with refractory dry eye disease (DED) often face the threat of diminished visual quality and have limited responses to existing treatments. Ocular injection Mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for DED. Topical drops are clinical favorable choice drug administration in To date, use MSC not been reported settings. This trial represents groundbreaking exploration into preliminary potential safety umbilical cord patients DED, including both non-Sjögren's (NSDE) Sjögren's syndrome (SSDE). The study also aimed investigate possible underlying mechanisms. In this open-label, prospective, single-arm, self-controlled trial, 11 NSDE 5 SSDE received twice-daily two weeks, subsequent follow-up visits were scheduled at 4 weeks 12 months after treatment. primary efficacy was evaluated using ocular surface index (OSDI) score, tear meniscus height (TMH), non-invasive break-up time (NIBUT), Schirmer I test (SIT), corneal fluorescein staining (CFS) score. Secondary assessments focused on evaluation lipid layer, meibomian gland function, bulbar conjunctival redness. Safety monitored by recording adverse events (AEs) throughout study. Changes levels interleukin-6 (IL-6), IL-17A, Mucin 5AC (MUC5AC), C-C chemokine ligand 20 (CCL20) IL-23, along proteomic alterations, compared between baseline T-week2. Significant improvements observed most symptoms signs following treatment patients, particularly production measured SIT TMH, alleviation blockage. effect OSDI, NIBUT, layer more pronounced SSDE. No serious AEs during period. Post-treatment reductions IL-6 an increase MUC5AC, further confirmed efficacy. Tear analysis indicated that is associated inhibition inflammation caused T helper 17 (Th17) groups. prospective exploratory study, we demonstrated might offer manageable treating DED first time, potentially bringing perspective such patients. Our research endeavor, paving way future large-scale randomized positive-controlled trials. ClinicalTrials.gov, NCT05784519. Registered 28 February 2023, https://clinicaltrials.gov/study/NCT05784519 .

Language: Английский

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MANF inhibits Sjögren's syndrome salivary gland epithelial cell apoptosis and antigen expression of Ro52/SSA through endoplasmic reticulum stress/autophagy pathway

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 122, P. 110582 - 110582

Published: June 30, 2023

Language: Английский

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Therapeutic Targets in the Management of Dry Eye Disease Associated with Sjögren’s Syndrome: An Updated Review of Current Insights and Future Perspectives

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1777 - 1777

Published: March 20, 2024

Dry eye disease (DED) is a continuing medical challenge, further worsened in the autoimmune inflammatory hyperactivation milieu of Sjögren's syndrome (SS) due to disturbances innate and adaptive immunity with malfunctioning neuro-endocrine control. However, pathogenetic mechanisms SS DED are not fully established. This review summarized available evidence, from systematic reviews, meta-analyses, randomized clinical trials, for efficacy safety ocular therapeutics management DED. Relevant studies were obtained major databases using appropriate keywords. The largely empirical symptomatic, supportive, restorative treatments have significant limitations as they do alter local systemic progression. Topical therapies expanded include biologics, surgical approaches, scleral lens fitting, lid margin disease, treatments, nutritional support, transplantation stem cells. They curative, cannot permanently restore surface's homeostasis. These approaches efficacious short term most studies, more variability outcome measures among long term. offers an interdisciplinary perspective that enriches our understanding updated addresses current knowledge gaps identifies promising areas future research overcome this challenge.

Language: Английский

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Discovery and Verification of Sjögren’s Syndrome Protein Biomarkers in Tears by Targeted LC-MRM

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(6), P. 2219 - 2229

Published: April 29, 2024

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by exocrine gland dysfunction, mainly from the lacrimal and salivary glands. The disease causes severe aqueous dry eye (DED) associated with high rates of complications, including corneal ulceration, scaring, perforation. Systemic complications may occur as well a higher risk developing lymphoma. Diagnosis SS-DED often delayed difficult to establish. With aim discovering biomarkers help discriminate patients, combination untargeted targeted LC-MS/MS analyses were performed on tear samples collected Schirmer strips subjected tryptic digestion. Following analysis three cohorts development two LC-sMRM methods for verification putative found in first cohort samples, 64 proteins could be linked syndrome, hopes helping confirm diagnoses potentially stratifying severity these patients. Proteins that increased showed activation immune system alterations homeostasis. Several proteases protease inhibitors significantly changing SS-DED, consistent decrease specific known secreted gland.

Language: Английский

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Next-Generation Tear Meniscus Height Detecting and Measuring Smartphone-Based Deep Learning Algorithm Leads in Dry Eye Management

Ophthalmology Science, Journal Year: 2024, Volume and Issue: 4(5), P. 100546 - 100546

Published: May 7, 2024

This study aims to develop and assess an infrastructure using Python-based deep learning code for future diagnostic management purposes related dry eye disease (DED) utilizing smartphone images.

Language: Английский

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