This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazola...This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.展开更多
To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The...To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.展开更多
基金supported by a grant from National Natural Sciences Foundation of China (No.30873171)
文摘This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.
基金supported by the Natural Science Foundation of Fujian Province(Nos.2017J01822 and 2018J01347)Fujian Medical University(No.2017XQ1202)Fuzhou General Hospital(No.2017Q06)
文摘To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.
