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载有 5-FU 的 PLGA 微球自组装水凝胶作为一种新型的增生性玻璃体视网膜病变玻璃体替代物。

Self-assembling hydrogel loaded with 5-FU PLGA microspheres as a novel vitreous substitute for proliferative vitreoretinopathy.

机构信息

Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Department of Ophthalmology, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

J Biomed Mater Res A. 2020 Dec;108(12):2435-2446. doi: 10.1002/jbm.a.36995. Epub 2020 Jul 3.

DOI:10.1002/jbm.a.36995
PMID:32419359
Abstract

The vitreous substitute for proliferative vitreoretinopathy (PVR) surgery remains an unmet clinical need in ophthalmology. In our study, we developed an in situ formed hydrogel by crosslinking polyvinyl alcohol (PVA) and chitosan as a potential vitreous substitute. 5-fluorouracil (5-FU) Poly (lactic-co-glycolic acid) (PLGA) microspheres were developed and loaded onto the PVA/chitosan hydrogels to treat PVR. In vitro, PVA/chitosan hydrogels at four concentrations were subjected to morphological, physical, rheological analyses, and cytotoxicity was evaluated together with the characterization of 5-FU PLGA microspheres. In vivo, pharmacologically induce PVR rabbits were performed a vitrectomy. In the PVA group, 3% PVA/chitosan hydrogel was injected into the vitreous cavity. In the PVA/MS group, 3% PVA/chitosan hydrogel and 5-FU PLGA microspheres were injected. In the Control group, phosphate-buffered saline was injected. Therapeutic efficacy was evaluated with postoperative examinations and histological analyses. This study demonstrated that the 3% PVA/chitosan hydrogel showed properties similar to those of the human vitreous and could be a novel in situ crosslinked vitreous substitute for PVR. Loading 5-FU PLGA microspheres onto this hydrogel may represent an effective strategy to improve the prognosis of PVR.

摘要

用于增生性玻璃体视网膜病变 (PVR) 手术的玻璃体替代物仍然是眼科领域未满足的临床需求。在我们的研究中,我们通过交联聚乙烯醇 (PVA) 和壳聚糖开发了一种原位形成的水凝胶,作为一种潜在的玻璃体替代物。我们还开发了载有 5-氟尿嘧啶 (5-FU) 的聚乳酸-共-羟基乙酸 (PLGA) 微球,并将其负载到 PVA/壳聚糖水凝胶上以治疗 PVR。在体外,我们对四种浓度的 PVA/壳聚糖水凝胶进行了形态学、物理和流变学分析,并评估了细胞毒性以及 5-FU PLGA 微球的特性。在体内,通过玻璃体切除术对药理学诱导的 PVR 兔进行了实验。在 PVA 组中,将 3% PVA/壳聚糖水凝胶注入玻璃体腔。在 PVA/MS 组中,将 3% PVA/壳聚糖水凝胶和 5-FU PLGA 微球注入。在对照组中,注射磷酸盐缓冲盐水。通过术后检查和组织学分析评估治疗效果。本研究表明,3% PVA/壳聚糖水凝胶具有类似于人玻璃体的特性,可能成为治疗 PVR 的新型原位交联玻璃体替代物。将 5-FU PLGA 微球负载到这种水凝胶上可能代表改善 PVR 预后的有效策略。

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