PDF(Pubmed)
Abstract：
Systemic cryptococcosis is often fatal even with the current antifungal therapy and there is no vaccine available. Induction therapy with amphotericin B (AmB) is essential for its treatment, which can be either in the form of AmB deoxycholate at 1 mg/kg/day for 7 days or a single dose of liposomal AmB (AmB-LLs) at 10 mg/kg, both in combination with flucytosine. AmB is highly toxic and it is imperative to further increase its efficacy without increasing its toxicity. Previously, we developed a targeted antifungal drug delivery system (DectiSome) that uses liposomes decorated with host-pathogen receptor dectins to target AmB to fungal cells. Here, we showed that a single dose of Dectin-2 coated liposomal AmB, relative to AmB-LLs, reduced fungal burden and prolonged animal survival in the murine model of systemic cryptococcosis. Our results demonstrate that DectiSomes are a promising antifungal delivery system that could improve cryptococcosis therapy in the future.
摘要：
即使使用当前的抗真菌治疗，系统性隐球菌病通常也是致命的，并且没有可用的疫苗。两性霉素B（AmB）的诱导治疗对其治疗至关重要，可以是1mg/kg/天的AmB脱氧胆酸盐形式，持续7天，也可以是10mg/kg的单剂量脂质体AmB（AmB-LLs），两者都与氟胞嘧啶结合。AmB是高毒性的,并且必须进一步增加其功效而不增加其毒性。以前,我们开发了一种靶向抗真菌药物递送系统（DectiSome），该系统使用装饰有宿主病原体受体dectin的脂质体将AmB靶向真菌细胞。这里,我们发现单剂量的Dectin-2包被的脂质体AmB，相对于AmB-Ll,在系统性隐球菌病鼠模型中减少真菌负担和延长动物存活。我们的结果表明，DectiSomes是一种有前途的抗真菌递送系统，可以在未来改善隐球菌病的治疗。
