Construction and Preliminary Evaluation of Lipid Complex of siRNA Modified by D-α-tocopheryl Poly (2- ethyl-2-oxazoline) Succinate / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare small interfering RNA(siRNA) lipid complexes (TPOS-L/siRNA) modified by D-α-tocopheryl poly (2-ethyl-2-oxazoline) succinate (TPOS). METHODS: The conventional siRNA lipid complexes (CLs /siRNA) and PEGylated CLs /siRNA (PEG-L/siRNA) were used as controls. CLs /siRNA was prepared by mixing blank CLs and siRNA directly of equal volume according to the electrostatic interaction of positive and negative charges. The encapsulation efficiency, morphology, stability, in vitro release and cell uptake of TPOS-L/siRNA were investigated. RESULTS: The CLs/siRNA had obvious lipid bilayer structure, the encapsulation efficiency (EE) was (86.68 ± 1.41)%, and the particle size of CLs /siRNA was less than 200 nm. The modification with TPOS or PEG-DSPE had no significant effect on the EE and particle size of CLs /siRNA, which could endow the lipid complexes with good stability. In addtion, TPOS-L/siRNA had good pH-sensitive property, and could respond to slightly acidic environment, which significantly enhanced the cell uptake. CONCLUSION: TPOS can construct good siRNA carrier and increase the stability and pH sensitivity of the nanocarrier.