RRC ID 81929
Author Otake H, Kobayashi K, Kadowaki R, Kosaka T, Itahashi M, Tsubaki M, Matsuda M, Iwakiri N, Harata E, Nagai N.
Title Copolymerized Polymers Based on Cyclodextrins and Cationic Groups Enhance Therapeutic Effect of Rebamipide in the N-Acetylcysteine-Treated Dry Eye Model.
Journal Drug Des Devel Ther
Abstract PURPOSE:We aimed to prepare a β-cyclodextrin (β-CD) polymer 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, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye.
METHODS:The β-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model).
RESULTS: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.
Volume 18
Pages 4345-4358
Published 2024-1-1
DOI 10.2147/DDDT.S469445
PII 469445
PMID 39359484
PMC PMC11445867
MeSH Acetylcysteine* / administration & dosage Acetylcysteine* / chemistry Acetylcysteine* / pharmacology Alanine* / administration & dosage Alanine* / analogs & derivatives Alanine* / chemistry Alanine* / pharmacology Animals Cations / chemistry Cornea / drug effects Cornea / metabolism Cyclodextrins / chemistry Cyclodextrins / pharmacology Disease Models, Animal* Dry Eye Syndromes* / drug therapy Humans Male Molecular Structure Polymerization Polymers / chemistry Polymers / pharmacology Quinolones* / administration & dosage Quinolones* / chemistry Quinolones* / pharmacology Rabbits Rats Solubility beta-Cyclodextrins / chemistry
Resource
Human and Animal Cells HCE-T(RCB1384)