Cytotoxicity and permeability enhancement of Capmul®MCM in nanoemulsion formulation

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. ¹⁴C-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 ¹⁴C-mannitol and ³H-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.