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载螺旋霉素 PLGA 植入物治疗眼弓形虫病:研制、特性、生物相容性和抗弓形虫活性。

Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

机构信息

Department of Biotechnology, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil.

School of Pharmacy, Federal University of Ouro Preto, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Pharmazie. 2021 Feb 25;76(2):68-76. doi: 10.1691/ph.2021.0100.

DOI:10.1691/ph.2021.0100
PMID:33714282
Abstract

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of efficacy against . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

摘要

眼弓形体病是全球感染性后葡萄膜炎的主要原因,可导致视野缺损和/或失明。尽管这种疾病很严重,但仍缺乏有效的治疗方法。在这项研究中,开发了载螺旋霉素的 PLGA 植入物,旨在治疗眼弓形体病。植入物采用热成型技术制造,通过傅里叶变换红外光谱、X 射线衍射、差示扫描量热法、扫描电子显微镜进行表征;通过免疫荧光、流式细胞术、细胞迁移、鸡胚绒毛尿囊膜(HET-CAM)刺激性试验评估其眼部生物相容性;并研究其对 的疗效。表征技术表明,螺旋霉素分散在聚合物链中,两种物质在植入物中均保持其物理结构。HET-CAM 试验表明,植入物不会引起出血或凝血,对 CAM 无刺激性。MTT 法检测 ARPE-19 细胞显示活力,细胞周期动力学和形态正常,不会通过细胞凋亡刺激细胞死亡。最后,它们对细胞内寄生虫非常有效,而不会导致人视网膜色素上皮细胞死亡。总之,载螺旋霉素的 PLGA 植入物为眼弓形体病的局部治疗提供了一种有前途的治疗选择。

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