Project description:Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.

| S-EPMC7376230 | biostudies-literature

Correction: Use of biomaterials for sustained delivery for anti-VEGF to treat retinal diseases.

Project description:An amendment to this paper has been published and can be accessed via a link at the top of the paper.

| S-EPMC7468361 | biostudies-literature

Microporous Drug Delivery System for Sustained Anti-VEGF Delivery to the Eye.

Project description:PurposeTo describe a novel microporous drug delivery system (DDS) for sustained anti- vascular endothelial growth factor (VEGF) delivery to the eye and to evaluate its efficacy in a corneal injury model.MethodsA macro-porous DDS (1.5 × 1.5 × 4 mm) loaded with 2 mg of bevacizumab was implanted subconjunctivally in three Dutch-belted pigmented rabbits after corneal alkali injury (2N NaOH). Three rabbits received sham DDS. Animals were followed for three months and assessed in vivo and ex vivo for corneal neovascularization (NV), epithelial defect, stromal scarring, endothelial cell loss, and expression of angiogenic and inflammatory markers in the cornea and retina.ResultsAnti-VEGF DDS treatment led to complete inhibition of superior cornea NV and complete corneal re-epithelialization by day 58 whereas sham DDS resulted in severe cornea NV and persistent epithelial defect (9%∼12% of total cornea area) through the end of the study. Histologically, anti-VEGF DDS significantly reduced CD45+ and F4/80 CD11b+ cell accumulation (79%, P < 0.05) in the cornea, ameliorated tumor necrosis factor-α expression (90%, P < 0.05), reduced corneal stromal scarring and prevented corneal endothelial cell loss, as compared to sham DDS. Moreover, anti-VEGF DDS achieved retinal penetration and reduction in retinal VEGF levels at 3 months.ConclusionsUse of subconjunctival anti-VEGF DDS suppresses cornea NV, inflammation, stromal scarring, prevents endothelial cell loss, and abrogates retinal VEGF upregulation in a rabbit corneal alkali burn model. Moreover, it delivers anti-VEGF antibodies to the retina for three months. This delivery platform could enable antibody therapy of other corneal and retinal vascular pathologies.Translational relevanceWe describe a method for sustained anti-VEGF delivery to the eye for the treatment of ocular injuries.

| S-EPMC7422759 | biostudies-literature

Silk-based biomaterials for sustained drug delivery.

Project description:Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk's well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products.

| S-EPMC4142080 | biostudies-other

Comment on: Disentangling the association between retinal non-perfusion and anti-VEGF agents in diabetic retinopathy.

Project description: Not available

| S-EPMC9307818 | biostudies-literature

Epigenetic modifiers to treat retinal degenerative diseases.

Project description:We have previously demonstrated the ability of inhibitors of LSD1 and HDAC1 to block rod degeneration, preserve vision, maintain rod-specific transcripts and downregulate those involved in inflammation, gliosis, and cell death in the rd10 mouse model of Retinitis Pigmentosa (RP). To extend our findings we tested the hypothesis that broad range of inhibitors of chromatin condensation can prevent photoreceptor degeneration in the rd10 mouse model. We used inhibitors for G9A/GLP that catalyzes methylation of H3K9, for EZH2 that catalyzes trimethylation of H3K27 and compared them to the actions of LSD1 and HDAC inhibitors. All the inhibitors decondense chromatin and all preserve, to different extents, retinas from degeneration in rd10mice, but they act through different metabolic pathways. One group of inhibitors, modifiers for LSD1 and EZH2, demonstrate a high level of maintenance of rod-specific transcripts, activation of Ca+2 and Wnt signaling pathways with inhibition of antigen processing and presentation, immune response and microglia phagocytosis. Another group of inhibitors, modifiers for HDAC and G9A/GLP work through upregulation of NGF-stimulated transcription, while down-regulating genes belong to immune response, extracellular matrix, cholesterol signaling and programmed cell death.

2025-05-13 | GSE295538 | GEO

Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options.

Project description:Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15-40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

| S-EPMC8145407 | biostudies-literature

Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous.

Project description:Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature-a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.

| S-EPMC10141348 | biostudies-literature