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载环孢素 A 的聚乳酸-聚己内酯/热塑性聚氨酯基质作为马免疫介导性角膜炎(IMMK)的治疗平台。

PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses.

机构信息

Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.

International Institute of Translational Medicine, Jesionowa 11 St., 55-124 Malin, Poland.

出版信息

Int J Mol Sci. 2023 Mar 17;24(6):5735. doi: 10.3390/ijms24065735.

Abstract

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK.

摘要

本研究的目的是描述用富含环孢素 A(CsA)的聚乳酸-乙醇酸共聚物/热塑性聚氨酯(PLDLA/TPU)基质作为治疗平台,用于治疗免疫介导性角膜炎(IMMK)的马匹。该平台在体外评估 CsA 的释放和降解情况,并在动物模型中确定该平台的安全性和疗效。我们研究了由热塑性聚氨酯(TPU)聚合物和聚 L-乳酸与 DL-乳酸(PLDLA)(80:20)的共聚物构成的 TPU(10%)和 PLDL(90%)聚合物共混物的 CsA 释放动力学。此外,我们使用 37°C 的 STF(模拟泪液)作为生物环境来评估 CsA 的释放及其降解。此外,在诊断为浅表和中基质层 IMMK 的马匹处于镇静状态下,将上述平台注射到眼球的背外侧象限的结膜下。结果表明,与前几周相比,研究第五周的 CsA 释放率显著增加了 0.3%。在所有情况下,用 12mg CsA 掺杂的 TPU/PLA 平台有效减轻了角膜炎的临床症状,导致角膜混浊和浸润在注射后四周完全消退。本研究结果表明,富含 CsA 平台的 PLDLA/TPU 基质被马模型耐受良好,并能有效治疗浅表和中基质层 IMMK。

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