Formulation development and in vitro evaluation of transferrin-conjugated liposomes as a carrier of ganciclovir targeting the retina
Formulation development and in vitro evaluation of transferrin-conjugated liposomes as a carrier of ganciclovir targeting the retina
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DOI：
10.1016/j.ijpharm.2020.119084
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发表时间：
2020-03-15
影响因子：
5.8
通讯作者：
Fuongfuchat, Asira
中科院分区：
文献类型：
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作者：
Asasutjarit, Rathapon;Managit, Chittima;Fuongfuchat, Asira
更昔洛韦（GCV）是一种抗病毒药物，被批准用于治疗巨细胞病毒（CMV）视网膜炎。它可以通过全身给药递送至眼睛。然而，靶向视网膜的GCV局部给药被认为是提高治疗效果并减少副作用的替代方案。因此，本研究旨在开发用于玻璃体内注射和局部滴注的含有GCV的转铁蛋白（Tf）缀合的脂质体（Tf-GCV-LPs）的制剂。通过反相蒸发技术制备Tf-GCV-LP，然后与Tf缀合。对其理化性质进行了评价。筛选出最佳处方，并进行细胞毒性试验、人视网膜色素上皮细胞（ARPE-19细胞）摄取研究和抗病毒活性评价。结果表明，转铁蛋白GCVLPs的理化性质受制剂组成的影响。优化的Tf-GCV-LP具有小于100 nm的粒径和负值的zeta电位。它们对ARPE-19细胞是安全的。这些Tf-GCV-LP通过Tf受体介导的内吞作用被这些细胞摄取，并在感染的细胞中显示出对CMV的抑制活性。因此，优化的Tf-GCV-LPs可以被接受作为一个有前途的药物递送系统，用于靶向GCV递送到视网膜治疗CMV视网膜炎。
Ganciclovir (GCV) is an antiviral drug approved for treatment of cytomegalovirus (CMV) retinitis. It can be delivered to the eye via systemic administrations. However, local delivery of GCV that targets the retina is considered as an alternative to increase efficacy of the treatment and lessen side effects. Thus, this study aimed to develop formulations of transferrin (Tf)-conjugated liposomes containing GCV (Tf-GCV-LPs) for intravitreal injection and topical instillation. Tf-GCV-LPs were prepared by the reverse-phase evaporation technique and then conjugated to Tf. Their physicochemical properties were evaluated. The optimized formulation was selected and subjected to the cytotoxicity test, cellular uptake study in the human retinal pigment epithelial cells (the ARPE-19 cells) and antiviral activity evaluation. The results showed that physicochemical properties of Tf-GCVLPs were affected by formulation compositions. The optimized Tf-GCV-LPs had a particle size lower than 100 nm with a negative value of zeta potential. They were safe for the ARPE-19 cells. These Tf-GCV-LPs were taken up by these cells via Tf receptors-mediated endocytosis and showed inhibitory activity on CMV in the infected cells. Therefore, the optimized Tf-GCV-LPs could be accepted as a promising drug delivery system for targeted GCV delivery to the retina in the treatment of CMV retinitis.