New targets and delivery systems for antifungal therapy
New targets and delivery systems for antifungal therapy
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DOI：
10.1080/mmy.38.s1.335.347
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发表时间：
2000-01-01
期刊：
影响因子：
2.9
通讯作者：
Odds, FC
中科院分区：
文献类型：
--
作者：
Walsh, TJ;Viviani, MA;Odds, FC
侵袭性真菌感染治疗新方法的发展包括已批准和正在研究的化合物的新递送系统，以及利用细胞膜、细胞壁和毒力因子作为假定的抗真菌靶点。由环糊精、耳蜗酸盐、纳米颗粒/纳米球和长循环（“隐形”）脂质体组成的新型给药系统，实质上调节了现有化合物的药代动力学，也可能有助于增强抗真菌药物对感染部位的递送。针对真菌细胞膜中麦角甾醇生物合成的抗真菌三唑的结构-活性关系的进一步研究导致了高效广谱药物的开发，包括泊沙康唑、拉武康唑和伏立康唑。类似地，新一代细胞壁活性半合成针叶白菌素1,3 β -葡聚糖抑制剂（caspofungin， FK463和VER-002）已进入临床开发。这些制剂对念珠菌具有强效的广谱活性，对曲霉菌和卡氏肺囊虫具有潜在的有效活性。分子发病机制、抗真菌药理学和疫苗开发领域的持续融合将为开发新的靶点提供机会，以补充现有的抗真菌药物。
Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta -glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium.