Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, India.
National Institute of Biologicals, NOIDA, Uttar Pradesh 201309, India.
Int J Pharm. 2021 May 1;600:120484. doi: 10.1016/j.ijpharm.2021.120484. Epub 2021 Mar 15.
Natamycin is the only FDA approved drug that is used as a first line of treatment for fungal keratitis caused by filamentous fungi, however natamycin is known for poor corneal penetration. Cell penetrating peptides (CPPs) are emerging nanocarriers for the enhanced delivery of various macromolecules owing to their distinct cellular translocation ability. In the present study, tissue penetration ability and antifungal efficacy of CPP (Tat) conjugated natamycin has been investigated and compared with natamycin alone in vivo. Results show that Tatnatamycin exhibits five- fold higher ocular penetration than natamycin alone when given topically. Complete resolution of fungal keratitis in 44% of the animals in Tatnatamycin treated group as compared to only 13% of the animals in natamycin treated group further highlights its increased antifungal efficacy. Hence, this conjugate is a promising antifungal molecule with enhanced ocular penetration as well as antifungal efficacy against selected fungal species.
纳他霉素是唯一一种被美国食品药品监督管理局批准的药物，可作为治疗丝状真菌引起的真菌性角膜炎的一线药物，然而，纳他霉素的角膜穿透性很差。细胞穿透肽（CPPs）是新兴的纳米载体，由于其独特的细胞转运能力，可用于增强各种大分子的递送。在本研究中，研究了 CPP（Tat）缀合纳他霉素的组织穿透能力和抗真菌功效，并与单独使用纳他霉素进行了体内比较。结果表明，局部给予 Tatnatamycin 后，其眼内穿透率是单独使用纳他霉素的五倍。在 Tatnatamycin 治疗组中，有 44%的动物完全消除了真菌性角膜炎，而在纳他霉素治疗组中，只有 13%的动物完全消除了真菌性角膜炎，这进一步突出了其增强的抗真菌功效。因此，该缀合物是一种有前途的抗真菌分子，具有增强的眼部穿透性和对选定真菌物种的抗真菌功效。
