Posted by β-cyclodextrin polymers were prepared using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-β-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug were evaluated, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye using a rabbit treated with N-acetylcysteine (dry eye model).
Rebamipide (REB) is a quinolinone derivative with mucin secretagog activity, and the biological effects include prevention of inflammation, wound healing, and cytoprotection in various tissues.
The solubility of the CDQA powder was higher than that of the β-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the β-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation.
Conclusion: The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.
Otake H, Kobayashi K, Kadowaki R, Kosaka T, Itahashi M, Tsubaki M, Matsuda M, Iwakiri N, Harata E, Nagai N. Copolymerized Polymers Based on Cyclodextrins and Cationic Groups Enhance Therapeutic Effect of Rebamipide in the N-Acetylcysteine-Treated Dry Eye Model. Drug Des Devel Ther. 2024;18:4345-4358
https://doi.org/10.2147/DDDT.S469445