他克莫司纳米新剂型的研究与应用

Research and Application of Tacrolimus Nano-formulations

关键词:  他克莫司  眼  给药系统

Key words:  tacrolimus  eye  drug delivery system

摘要:

他克莫司 (tacrolimus,TAC) 是一种从筑波链霉菌中分离出来的脂溶性免疫抑制剂,能通过阻断钙调神经磷酸酶和IL-2基因转录的活性来抑制白细胞介素-2的产生,从而抑制T淋巴细胞反应,还能抑制炎症细胞因子的释放,这些机制有助于TAC治疗干眼症、春季角膜结膜炎和角膜新生血管等疾病。由于其在水中的溶解度较差 (0.67±0.19 μg/mL),难以制成传统普通的眼用剂型。近年来,为了克服TAC溶解度差的难题,开发出各种眼部新型给药系统,如脂质体、原糖体纳米囊泡、聚合物胶束、纳米乳、纳米粒、水凝胶、环糊精包合物、微晶等,用于治疗各种眼部的疾病,有巨大的临床应用潜力。笔者对近几年TAC新型眼部制剂及其对眼病的治疗做一综述,以便为其研发提供参考。

Abstract:

Tacrolimus (TAC) is an immunosuppressant isolated from Streptomyces tsukubaensis that acts as a lipophilic immunosuppressant. Its inhibitory effects extend to the production of interleukin-2 through the blockade of calmodulin neural phosphatase and IL-2 gene transcription, consequently suppressing T-lymphocyte responses. Additionally, TAC impedes the release of inflammatory cytokines. These multifaceted mechanisms enable TAC to effectively manage conditions such as dry eye, spring keratoconjunctivitis, and corneal neovascularisation. Given its limited solubility in water (0.67±0.19 μg/mL), TAC poses a challenge for formulation into conventional ophthalmic dosage forms. In an effort to surmount the solubility issue of TAC, recent years have witnessed the development of innovative ocular drug delivery systems for TAC. These delivery systems including liposomes, proglycosome nanovesicles, polymer micelles, nanoemulsions, nanoparticles, hydrogels, cyclodextrin inclusion compounds, and microcrystals, all of which are designed for the treatment of a range of ocular disorders and demonstrate considerable potential for application. The objective of this study is to critically review recent developments in the novel ocular formulations of TAC for the treatment of ocular diseases, thereby providing a comprehensive reference for future research and development in this field.