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Imatinib@glycymicelles entrapped in hydrogel: preparation, characterization, and therapeutic effect on corneal alkali burn in mice

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Abstract

Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55 μg/mL to bare IMB to 359,967.62 ± 20,059.42 μg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage.

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The data and materials of this study are available on reasonable request.

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Funding

This research was supported by the Natural Science Foundation of Shandong Province (Grant No. ZR2023MH343), and the Medicine Science and Technology Development Program of Shandong Province (Grant No. 202107020108).

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Authors and Affiliations

  1. College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China

    Yanan Wang, Shaohua Shi, Songtao Wang, Hongqing Qin, Yanjun Wei & Xianggen Wu

  2. Deparment of Pathology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China

    Yanan Wang & Mengmeng Zhang

  3. Qingdao Women and Children’s Hospital, Qingdao, China

    Ling Zhang

  4. Viwit Pharmaceutical Co., Ltd. Zaozhuang, Shandong, China

    Yanjun Wei & Xianggen Wu

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  1. Yanan Wang
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Contributions

Yanan Wang: Investigation, Methodology, Validation, Writing—original draft. Shaohua Shi: Investigation, Methodology. Ling Zhang: Investigation, Methodology. Songtao Wang: Investigation, Methodology. Hongqing Qin: Investigation, Methodology. Yanjun Wei: Investigation, Methodology. Xianggen Wu: Conceptualization, Funding acquisition. Mengmeng Zhang: Conceptualization, Funding acquisition, Project administration, Resources, Writing—review & editing.

Corresponding authors

Correspondence to Xianggen Wu or Mengmeng Zhang.

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Ethics approval and consent to participate

Male C57BL/6 mice (eight weeks old) were taken from Jinan Pengyue Experimental Animal Breeding Co., Ltd. (Jinan, China), and New Zealand white rabbits were procured from Qingdao Kangda Foodstuffs Co., Ltd. (Qingdao, China). Animal care and the procedures used were in accordance with the Guide for the Care and Use of Laboratory Animals. This animal experiment was conducted under a protocol approved by the Ethics Committee for Animal Experimentation of Qingdao University of Science and Technology (approval document No. 2022–1116, Qingdao, China).

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Wang, Y., Shi, S., Zhang, L. et al. Imatinib@glycymicelles entrapped in hydrogel: preparation, characterization, and therapeutic effect on corneal alkali burn in mice. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01570-5

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