![]() In practice, however, NAT and CLZ presented the disadvantages of low water solubility, rapid metabolism, and high dosing frequency, thus limiting their therapeutic potential. Therefore, it has been hypothesized that the combination of NAT with CLZ might have a synergistic effect upon the treatment of FK. In addition, CLZ also has the capability to interfere with the transformation of Candida albicans from the spore form to the invasive hyphae ( Adams, 1990 Govender, 2015). In particular, clotrimazole (CLZ) kills the fungal cell by inhibiting the biosynthesis of triglycerides and phospholipids along with the activity of oxidase and peroxidase, making this a broad-spectrum antimycotic drug. Despite its worldwide use in the treatment of FK, a long treatment time is incurred when NAT is used alone and, hence, adjuvant therapy with other drugs is usually required. The antifungal mechanism of NAT is to damage the permeability of the cell membrane by binding with ergosterol and to disrupt the normal metabolism and growth of the fungus. Meanwhile, natamycin (NAT) is the only topical ophthalmic drug with powerful antifungal effects and few side effects that has been approved by the Food and Drug Administration (FDA) ( Dietrich, 2010 Mimouni et al., 2014). The main fungal species, causing corneal fungal inflammation, are Fusarium, Aspergillus, and Candida, with Candida being one of the most important pathogenic fungi. Moreover, its relatively high prevalence makes it a very serious burden for health care systems around the tropical regions such as South India, Ghana, and China ( Roy et al., 2019). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.įungal keratitis (FK) is a major form of inflammation that is accompanied by vision loss and blindness ( Chodosh, 2011 Liu et al., 2013). Thus, good biosafety along with a significant anti-candidiasis effect are found in the nanoparticles (NPs). Furthermore, in vitro hemolysis, in vivo corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. The resulting formulations were characterized by a transmission electron microscope (TEM) and in vitro release test. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). 4Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, China.3Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.2Department of Pharmacy, Weifang Traditional Chinese Hospital, Weifang, China.1College of Pharmacy, Weifang Medical University, Weifang, China.Xiaoming Cui 1, Xiaoli Li 2, Zhilu Xu 1, Xiuwen Guan 1,3,4, Jinlong Ma 1,3,4, Dejun Ding 1,3,4* and Weifen Zhang 1,3,4*
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