In Vitro and In Vivo Studies of Polyvinyl Pyrrolidone-Coated Sparfloxacin-Loaded Ring Contact Lens to Treat Conjunctivitis.

Currently, conjunctivitis is treated by frequent high dose administration of sparfloxacin eye drop solution. However, the eye drops are inconvenient because of low bioavailability, short ocular drug residence time, and need of frequent instillation, which lead to patient noncompliance affecting the routine life style of patients. Silicone contact lenses can be used to sustain the release of sparfloxacin. However, the presence of sparfloxacin alters the optical and physical properties of the contact lens. To overcome the issues, a novel polyvinyl pyrrolidone (PVP)-coated sparfloxacin-laden ring contact lens was designed to provide sustained ocular drug delivery without altering the optical and swelling properties of contact lens. The ring was implanted within the periphery of the lens. Sparfloxacin was loaded by soaking (Sp-S), direct loading (Sp-L), and ring casting method (Sp-R). PVP (comfort agent) was coated on the surface of contact lens by novel short surface curing technique. The in vitro sparfloxacin release data of Sp-S (up to 12-36 h) and Sp-L batches (up to 12-24 h) showed high burst release, whereas Sp-R batch showed sustained release up to 36-48 h without significant (p > 0.05) alteration of the optical and swelling properties. All the batches showed sustained release of PVP up to 48 h. The in vivo release studies in the rabbit tear fluid showed improvement in the sparfloxacin [>MIC for Staphylococcus aureus] and PVP retention time in comparison to eye drop solution. The in vivo efficacy study in the S aureus-induced conjunctivitis showed improved healing effect with the single PVP-coated Sp-R-300 contact lens in comparison to the frequent high-dose sparfloxacin eye drop therapy. The study demonstrated the successful application to codeliver sparfloxacin and PVP from the contact lens for the extended period to treat conjunctivitis.

TGF-ß2 stimulates Tenon's capsule fibroblast proliferation in patients with glaucoma via suppression of miR-29b expression regulated by Nrf2.

PURPOSE: To investigate the role of transforming growth factor-ß2 (TGF-ß2) in Tenon's capsule fibroblasts proliferation from glaucoma patients and the effect of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and miR-29b mRNA in this process. METHODS: Tenon's capsule fibroblasts obtained from patients who had undergone selective glaucoma surgery (GTFs) were cultured and stimulated with 5 ng/mL TGF-ß2 for 1, 3, 5, and 7 days. MTS assay was performed to detect the cell viability. Expression of Nrf2 and miR-29b was analyzed with western blot, RT-PCR and Chromatin immunoprecipitation assay (ChIP) in human fibroblast SX1412-B exposed to TGF-ß2. RESULTS: MTS assay showed that TGF-ß2 was more stimulatory on GTFs proliferation than controls. At the same time, TGF-ß2 exerted an intenser effect of decreasing the Nrf2 protein and miR-29b mRNA levels in GTFs, and the level of miR-29b was effectively regulated by Ad-Nrf2. In addition, ChIP assay suggested that TGF-ß2 down-regulated miR-29b expression through repressing the binding of Nrf2 to the promoter of miR-29b. Finally, we found that overexpression Nrf2 in GTFs reduced the proliferation effect on GTFs induced by TGF-ß2, while miR-29b inhibitor reversed this effect. CONCLUSION: This study suggests that TGF-ß2 has a time-effect relationship with Tenon's capsule fibroblasts proliferation from glaucoma patients, and it stimulates Tenon's capsule fibroblast proliferation via suppression of miR-29b expression regulated by Nrf2.