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A. Hugh-Bloch, M. Hornof, M. Hoffer, A. Clausen; Disulfide Crosslinked Hyaluronic Acid Films for Ocular Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5773. doi: https://doi.org/.
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To demonstrate the feasibility of producing disulfide crosslinked polymeric films using a novel thiolated hyaluronic acid derivative.
Hyaluronic acid (HA) was modified with thiol groups via the covalent attachment of cysteamine. Gel films were prepared by a casting technique using 1% (m/v) aqueous solutions of HA-Thiol adjusted to pH 5.5, 6.5 or 7.4. Some films were additionally crosslinked with hydrogen peroxide after drying. Films were cut into 5x5 to 8x8 mm patches for all further studies. HA-Thiol films were characterized with regard to their appearance, water content and the amount of free thiol groups after drying and their swelling and dissolution behavior in artificial tear fluid. In vitro release studies were conducted with diclofenac and bovine serum albumin (BSA) as model substances for ocular drug delivery.
The films were transparent, robust and flexible. After 40 h drying at 37°C the water content in the HA-Thiol films was negligible. The degree of crosslinking was monitored by measuring remaining free thiol groups in the gel films. Drying at pH 7.4 led to a higher degree of crosslinking via disulfide bonds than drying at pH 5.5. Films with a low degree of crosslinking dissolved in artificial tear fluid within minutes, whereas highly crosslinked films were stable for more than one week. Due to water uptake the size of the films increased 2- to 4-fold, while the original shape of the films was maintained. Additional crosslinking with H2O2 resulted in films with lower water uptake and no additional size increase. In vitro release of the model drugs diclofenac-sodium and BSA from the HA-Thiol films was complete after 2 to 3 h.
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