Pharmaceutical Nanotechnology Department, Shiraz University of Medical Sciences, Shiraz, PO Box 71345-1583, Iran.
Pharmaceutical Nanotechnology Department, Shiraz University of Medical Sciences, Shiraz, PO Box 71345-1583, Iran; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, PO Box 71345-1583, Iran.
Biomater Adv. 2022 Aug;139:212996. doi: 10.1016/j.bioadv.2022.212996. Epub 2022 Jun 22.
Although Amphotericin B (AMB) is considered the most effective anti-mycotic agent for treating Candida infections, its clinical use is limited due to its high toxicity. To address this issue, we developed cholesterol-based dendritic micelles of hyperbranched polyglycerol (HPG), including cholesterol-cored HPG (Chol-HPG) and cholesterol end-capped HPG (HPG@Chol), for AMB delivery. The findings suggested that the presence of cholesterol moieties could control AMB loading and release properties. Dendritic micelles inhibited AMB hemolysis and cytotoxicity in HEK 293 and RAW 264.7 cell lines while increasing antifungal activity against C. albicans biofilm formation. Furthermore, significantly lower levels of renal and liver toxicity biomarkers compared to Fungizone® ensured AMB-incorporated dendritic micelle biosafety, which was confirmed by histopathological evaluations. Overall, the Chol-HPG and HPG@Chol dendritic micelles may be a viable alternative to commercially available AMB formulations as well as an effective delivery system for other poorly soluble antifungal agents.
虽然两性霉素 B (AMB) 被认为是治疗念珠菌感染最有效的抗真菌药物，但由于其毒性高，其临床应用受到限制。为了解决这个问题，我们开发了基于胆固醇的支化聚甘油（HPG）的树状胶束，包括胆固醇核的 HPG（Chol-HPG）和胆固醇封端的 HPG（HPG@Chol），用于 AMB 的递送。研究结果表明，胆固醇部分的存在可以控制 AMB 的负载和释放特性。树状胶束抑制了 AMB 在 HEK 293 和 RAW 264.7 细胞系中的溶血和细胞毒性，同时增加了抗白色念珠菌生物膜形成的抗真菌活性。此外，与 Fungizone®相比，肾和肝毒性生物标志物的水平显著降低，确保了 AMB 结合的树状胶束生物安全性，这通过组织病理学评估得到了证实。总的来说，Chol-HPG 和 HPG@Chol 树状胶束可能是市售 AMB 制剂的可行替代品，也是其他难溶性抗真菌药物的有效递送系统。
