Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Drug Deliv Transl Res. 2022 Mar;12(3):662-675. doi: 10.1007/s13346-021-00974-x. Epub 2021 Apr 8.
Posaconazole (PSC) is a triazole group anti-fungal agent with the widest spectrum. Although there is no commercially available ocular dosage form, its diluted oral suspension preparation (Noxafil) is used as off-label in topical treatment of severe keratitis and sclerokeratitis in the clinic. However, ocular bioavailability of PSC suspension form is extremely low due to its highly lipophilic character. Thus, there is a clinical need to improve its ocular bioavailability and to develop novel delivery system for the treatment of ocular fungal infections. Herein, we studied ex vivo permeation, penetration, anti-fungal activity, and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) toxicity tests in order to assess ocular targeting of PSC micelles, which were optimized in our previous study. The results indicated that micellar carrier system increased the permeability of PSC to eye tissues. Micelles showed higher affinity to ocular tissues than that of commercial oral suspension of PSC (Noxafil). In vitro anti-fungal activity data also confirmed the efficacy of PSC loaded micellar formulations against Candida. albicans strains. The relative safety of the optimized micelles on the ocular tissue was shown with the HET-CAM toxicity test. In conclusion, micellar systems could be a promising strategy for the effective and safe delivery of PSC in the treatment of ocular fungal infections.
泊沙康唑（PSC）是一种三唑类抗真菌药物，具有最广泛的谱。虽然没有市售的眼部剂型，但它的稀释口服混悬剂制剂（Noxafil）在临床上被用作治疗严重角膜炎和硬化性角膜炎的标签外用药。然而，由于其高度亲脂性，PSC 混悬剂形式的眼部生物利用度极低。因此，临床上需要提高其眼部生物利用度，并开发用于治疗眼部真菌感染的新型给药系统。在此，我们研究了离体渗透、穿透、抗真菌活性和鸡胚绒毛尿囊膜（HET-CAM）毒性试验，以评估我们之前研究中优化的 PSC 胶束的眼部靶向性。结果表明，胶束载体系统增加了 PSC 对眼部组织的通透性。与市售 PSC 口服混悬剂（Noxafil）相比，胶束对眼部组织具有更高的亲和力。体外抗真菌活性数据也证实了载 PSC 胶束制剂对抗白色念珠菌菌株的功效。HET-CAM 毒性试验显示，优化后的胶束对眼部组织具有相对安全性。总之，胶束系统可能是治疗眼部真菌感染时有效和安全递送 PSC 的有前途的策略。
