Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Int J Pharm. 2019 Apr 20;561:289-295. doi: 10.1016/j.ijpharm.2019.03.010. Epub 2019 Mar 7.
This study aimed to investigate the following factors affecting the cytotoxicity of Capmul®MCM (C8/10MD) in self-emulsified nanoemulsions (SENs): concentration, triglycerides, and droplet size, and how these factors influence permeability of lipid droplets. Two triglycerides (C8T and C18T) and six formulations were used: SEN1(C18T:C8/10MD:Kolliphor®RH40 = 7:3:10, 257 nm), SEN2(C8T:C8/10MD:Kolliphor®RH40 = 1:1:2, 30 nm), SEN3(C18T:Kolliphor®RH40 = 1:4, 26 nm), SEN4(C8T:Kolliphor®RH40 = 1:4, 27 nm), SEN5(C8/10MD:Kolliphor®RH40 = 1:1, 120 nm) and SEN6(C8/10MD:Kolliphor®RH40 = 1:4, 15 nm). There was no cytotoxicity from SEN3-4 (5% preconcentrate), but there was concentration-dependent cytotoxicity from the SENs containing C8/10MD. The presence of triglycerides in SEN1-2 reduced the toxicity of C8/10MD as compared to SEN5-6. SEN2 and SEN6 showed higher toxicity than SEN1 and SEN5, respectively, due to the smaller size. C-Triolein-loaded droplets from SEN1 (0.45-0.6% C8/10MD) and SEN2 (0.3-0.6% C8/10MD) could permeate across the MDCK monolayer, resulted in intact droplets and radioactivity in the receiver chamber. The TEER was reduced as the C8/10MD concentration increased, and not recovered after 24 h from SEN1 (0.6% C8/10MD) and SEN2 (0.45-0.6% C8/10MD), resulted in significantly higher (p < 0.05) permeability of C-mannitol and H-propranolol compared to the treatment by the medium. In conclusion, Capmul®MCM caused concentration-dependent cytotoxicity and permeation enhancement, which were reduced with the presence of triglycerides and increase in droplet size.
本研究旨在探讨以下因素对 Capmul®MCM（C8/10MD）在自乳化纳米乳（SEN）中的细胞毒性的影响：浓度、甘油三酯和液滴大小，以及这些因素如何影响脂滴的通透性。使用了两种甘油三酯（C8T 和 C18T）和六种配方：SEN1（C18T：C8/10MD：Kolliphor®RH40=7：3：10，257nm）、SEN2（C8T：C8/10MD：Kolliphor®RH40=1：1：2，30nm）、SEN3（C18T：Kolliphor®RH40=1：4，26nm）、SEN4（C8T：Kolliphor®RH40=1：4，27nm）、SEN5（C8/10MD：Kolliphor®RH40=1：1，120nm）和 SEN6（C8/10MD：Kolliphor®RH40=1：4，15nm）。SEN3-4（5%预浓缩物）没有细胞毒性，但含有 C8/10MD 的 SEN 表现出浓度依赖性细胞毒性。SEN1-2 中的甘油三酯的存在降低了 C8/10MD 的毒性，与 SEN5-6 相比。由于尺寸较小，SEN2 和 SEN6 的毒性分别高于 SEN1 和 SEN5。从 SEN1（0.45-0.6% C8/10MD）和 SEN2（0.3-0.6% C8/10MD）加载 C-三油酸甘油酯的液滴可以穿过 MDCK 单层，导致完整的液滴和放射性物质在接收室中。随着 C8/10MD 浓度的增加，TEER 降低，并且在 24 小时后从 SEN1（0.6% C8/10MD）和 SEN2（0.45-0.6% C8/10MD）中无法恢复，导致 C-甘露醇和 H-普萘洛尔的通透性显著增加（p<0.05）与介质处理相比。总之，Capmul®MCM 引起浓度依赖性细胞毒性和渗透增强，这两种作用均随甘油三酯的存在和液滴尺寸的增加而降低。
