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Qiaozhi Lu, Jemin J. Chae, Qiongyu Guo, Iossif Strehin, Mehnaz Khan, Freddy A. Espinoza, Jianan Zhan, Oliver Schein, Morgana M. Trexler, Jennifer H. Elisseeff; Controlled Vancomycin Release from Chondroitin Sulfate - Polyethylene Glycol (CS-PEG) Tissue Adhesive for Treatment of Corneal Injuries. Invest. Ophthalmol. Vis. Sci. 2011;52(14):439.
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To create a dual-purpose ocular repair material for corneal injuries while releasing antibiotics to prevent post-traumatic infection.
In vitro vancomycin release. Vancomycin free base (V-FB) was prepared from vancomycin hydrochloride (V-HCl). To make 100 µl hydrogel, 20% w/v CS-NHS and PEG-(NH2)6 were mixed in equal volumes and 2% V-FB or V-HCl was loaded. Hydrogels were immersed in 1 ml PBS and incubated at 37ºC (n=3). PBS fractions were collected at various time points and the concentration of vancomycin was analyzed by HPLC. Kirby-Bauer test was performed to evaluate the activity of vancomycin released.In vivo application. To evaluate the material-tissue interaction, rabbit corneas (n=6) with or without injuries were treated with a 20% CS-PEG adhesive. Two types of corneal injuries were created with 8 mm Hessburg-Barron vacuum trephines: partial thickness defect and deepithelialization. Flurosecein dye and H&E staining were used for observing tissue adhesion and local tissue response.
In vitro vancomycin release. HPLC results demonstrated that vancomycin was successfully released from CS-PEG. The cumulative release profile of V-FB was significantly more sustained than that of V-HCl, which produced a burst release of 82% over the first 24 hours, compared to 68% for V-FB. Considering the mass released, V-FB exhibited a more stable trend. In day 3, the mass released from V-FB form was approximate 1.5-fold of the corresponding V-HCl form. Kirby-Bauer tests confirmed that the vancomycin released from both forms was functional.In vivo application. CS-PEG applied on both deep and superficial corneal injury models adhered well to the local tissue and served as an ocular adhesive. It remained on injured corneal tissue over 7 days, which is adequate for release of antibiotics, as determined in the in vitro study. In the uninjured group, where epithelium was intact, the adhesive detached within 1 day. Thus it is notable that only the damaged areas would bind with CS-PEG, and no attachment was found on the other areas of the cornea.
In vivo and in vitro data supports the efficacy of the biosynthetic CS-PEG ocular tissue adhesive formulation for the application to treat corneal injuries and release of vancomycin.
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