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Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery
摘要： Ocular drug delivery has been a well-known route for the drug administration for the treatment of ocular diseases. However, numerous anatomical and physiological barriers prevailing in the eye itself create considerable challenges for achieving the necessitated therapeutic efficacy along with ocular bioavailability. However, recent advances in nanoengineered strategies hold definite promises in terms of devising improved ophthalmic medicines for the effective drug delivery to target the sites with enhanced ocular bioavailability. Curcumin, a hydrophobic polyphenol yellow colored compound, and its metabolic reduced product, tetrahydrocurcumin (THC), have been known for their beneficial pharmacological functions, such as anti-inflammatory or anti-oxidant activities at various tissue sites. However, the low aqueous solubility of these compounds results in their poor bioavailability, thereby limiting their widespread application. Therefore, in the present study, we investigated the changes in drug solubility by forming inclusion complexes with different derivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineering curcumin or THC-loaded formulations to improve the stability of formulations during the storage. The formulations were characterized in terms of physicochemical properties and cellular permeability. The results demonstrated that the encapsulation of curcumin (or THC) into the HP-CDs significantly increased the drug solubility and enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs with improved bioavailability also induced anti-oxidant activity (SOD1, CAT1, and HMOX1) in higher levels in the ocular epithelial cells and showed oxidative protection effects in rabbit cornea tissues that will boost up their application in ocular medicine.
关键词： Ophthalmic formulation,Curcumin,Retinal pigmented epithelium,Cyclodextrins,Tetrahydrocurcumin,Cellular transport,Human corneal epithelium
更新于2025-11-21 11:24:58
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Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations
摘要： The transplantation of retinal cells has been studied in animals to establish proof of its potential benefit for the treatment of blinding diseases. Photoreceptor precursors have been grafted in animal models of Mendelian-inherited retinal degenerations, and retinal pigmented epithelial cells have been used to restore visual function in animal models of age-related macular degeneration (AMD) and recently in patients. Cell therapy over corrective gene therapy in inherited retinal degeneration can overcome the genetic heterogeneity by providing one treatment for all genetic forms of the diseases. In AMD, the existence of multiple risk alleles precludes a priori the use of corrective gene therapy. Mechanistically, the experiments of photoreceptor precursor transplantation reveal the importance of cytoplasmic material exchange between the grafted cells and the host cells for functional rescue, an unsuspected mechanism and novel concept. For transplantation of retinal pigmented epithelial cells, the mechanisms behind the therapeutic benefit are only partially understood, and clinical trials are ongoing. The fascinating studies that describe the development of methodologies to produce cells to be grafted and demonstrate the functional benefit for vision are reviewed.
关键词： retinitis pigmentosa,photoreceptors,retinal pigmented epithelium,age-related macular degeneration,cytoplasmic material transfer,induced-pluripotent stem cells
更新于2025-09-19 17:15:36
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The Effects of Anti‐VEGF and Kinin B1 Receptor Blockade on Retinal Inflammation in Laser‐Induced Choroidal Neovascularization
摘要： BACKGROUND AND PURPOSE Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease treated by anti-VEGF intravitreal injections. As inflammation has a potential pathological role in retinal degeneration, the pro-inflammatory kallikrein-kinin system might be a relevant alternative pharmacological target. The present study investigated the effects of anti-VEGF and anti-B1R treatments on the inflammatory mechanisms in a rat model of choroidal neovascularization (CNV). EXPERIMENTAL APPROACH Immediately after laser-induced CNV, Long-Evans rats were treated by eye-drop application of a B1R antagonist (R-954) or by intravitreal injection of B1R siRNA or anti-VEGF antibodies. The impact of treatments on gene expression of inflammatory mediators, CNV lesion regression, and the integrity of the blood-retinal barrier was measured ten days later in the retina. B1R and VEGF-R2 cellular localization was also investigated. KEY RESULTS The three treatments had significant inhibitory effects on CNV-induced retina alterations. Anti-VEGF and R-954 significantly alleviated CNV-induced upregulation of B1R, B2R, TNF-α, and ICAM-1. Anti-VEGF additionally reversed the upregulation of VEGF-A, VEGF-R2, HIF-1α, MCP-1 and VCAM-1, whereas R-954 inhibited gene expression of IL-1β and COX-2. Enhanced retinal vascular permeability was abolished by anti-VEGF and significantly reduced by R-954 and B1R siRNA treatments. Leukocyte adhesion was also impaired by anti-VEGF and B1R inhibition. B1R occurred on astrocytes and endothelial cells. CONCLUSION AND IMPLICATIONS B1R and VEGF pathways are both involved in retinal inflammation and damage in laser-induced CNV. The non-invasive and self-administration of B1R antagonists on the surface of the cornea by eye-drops might be an important asset for the treatment of AMD.
关键词： microglia,AMD,retinal pigmented epithelium,VEGF,kinin B1 receptor,retina,angiogenesis
更新于2025-09-16 10:30:52