A novel layered double hydroxide (LDH) nanoparticle/thermogel composite drug delivery system (DDS) for sustained release of brimonidine (Bri) has been designed, prepared, and characterized in this study for treatment of severe glaucoma. Brimonidine is first loaded onto LDH (Bri@LDH) nanoparticles, which are then dispersed in the thermogel consisting of plenty of micelles based on poly(dl-lactic acid-co-coglycolic acid)-polyethylene glycol-poly(dl-lactic acid-co-coglycolic acid) (PLGA-PEG-PLGA) copolymer. The Bri@LDH/Thermogel DDS containing 125.0 μg/g of brimonidine has been found to sustainably release the drug for up to 144 h, significantly extending the drug release period compared to that from Bri@LDH nanoparticles. The Bri@LDH/Thermogel DDS is not cytotoxic to human corneal epithelial cells and shows good biocompatibility. In vivo drug release from the special contact lens made of Bri@LDH/Thermogel DDS has been sustained for at least 7 days, which more effectively modulates the relief of intraocular pressure (IOP). Thus, the Bri@LDH/Thermogel DDS is a promising drug delivery alternative that can be used for treatment of severe glaucoma.
We successfully developed a subconjunctival delivery system of CsA using an injectable thermogel to inhibit post-surgical scar formation after glaucoma filtration surgery.
Citation: Dai Z, Yu X, Sun J, Sun X. Grooved glaucoma drainage devices that continuously deliver cyclosporine A decrease postsurgical scar formation in rabbit eyes. Invest Ophthalmol Vis Sci. 2017;58:169258: -170158: . DOI: 10.1167 PURPOSE. To study the functional outcomes of filtration surgery by implanting improved glaucoma drainage devices (GDDs) comprising surface grooves and a composite coating of cyclosporine A (CsA) and PLGA in experimental rabbit eyes.METHODS. Improved GDDs were designed and prepared by modifying normal GDD with surface grooves and a CsA-PLGA composite coating. Normal GDDs, grooved GDDs (G-GDDs), and GGDDs with a CsA-PLGA composite coating (CsA@G-GDD) were implanted into 18 rabbit eyes (six eyes per group). The intraocular pressure (IOP), bleb survival time, bleb morphology, and anterior chamber reactions were assessed for up to 12 weeks after GDD implantation. The IOPs were compared statistically among the three groups. Bleb morphology was quantified using the Indiana Bleb Appearance Grading Scale. Anterior chamber radiography was performed to check whether the filtrating pathway was blocked, and determine the drainage time and diffusion area of the contrast agent. Hematoxylin and eosin staining and immunohistochemistry were conducted to assess how the GDDs slowed or prevented scar formation.RESULTS. The improved GDDs were successfully prepared and implanted in 18 rabbit eyes without severe surgical complications. Bleb survival time was significantly longer and IOP was significantly lower in the G-GDD and CsA@G-GDD groups compared with the GDD group (all, P < 0.001). Blebs were significantly higher in the CsA@G-GDD group than in the GDD and G-GDD groups (P ¼ 0.003). Anterior chamber radiography revealed more unobstructed filtration channels in the CsA@G-GDD group than in the GDD group (P ¼ 0.032). Postsurgical scar formation was less extensive in the G-GDD and CsA@G-GDD groups than in the GDD group.CONCLUSIONS. Compared with the normal GDDs, G-GDDs with a CsA-PLGA coating inhibited postsurgical scar formation and improved the surgical success rate, and might represent an alternative to existing glaucoma filtration devices.Keywords: glaucoma drainage devices, cyclosporine A, groove, filtration surgery, scar formation G laucoma is characterized by elevated intraocular pressure (IOP) and frequently causes optic neuropathy. If left untreated, it causes chronic progressive degeneration of retinal ganglion cells and visual field loss.1,2 The treatment of glaucoma typically begins with topical medications and then filtering surgeries. 3 Glaucoma filtration surgery seeks to achieve incomplete healing to allow the aqueous humor to escape the eye, unlike other surgical procedures in which complete wound healing is desired. 4 Unfortunately, IOP often increases after surgery owing to scar formation in the wound field. The success rate of trabeculectomy was reported to be 64.7% over 5 years in eyes with open-angle glaucoma. 5 In complicated cases, implantation of a glaucoma drainage device (GDD) is...
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