Optimization of pH response and mitochondrial targeting bifunctional hyperoside liposomes by central composite design response surface methodology and its in vitro evaluation / 中草药

ABSTRACT

Objective: To optimize preparation of mitochondrial targeting hyperoside liposomes (DLD/Hyp-Lip), and study its stability in fetal bovine serum, in vitro release behavior and mitochondrial targeting. Methods: DLD/Hyp-lip was prepared by film dispersion method. Single factor experiment was carried out with entrapment efficiency and drug loading as indexes to investigate the effects of the ratio of phospholipids to hyperoside (Hyp) and DSPE-PEG (distearoyl phosphoethanolamine-polyethylene glycol) to DLD on DLD/Hyp-Lip. The formulation of DLD/Hyp-Lip was further optimized by central composite design response surface methodology. The appearance, size and potential of liposomes were observed by transmission electron microscope and particle size analyzer. The stability and drug release rate of liposomes in fetal bovine serum were evaluated by serum stability test and in vitro drug release test. The drug delivery system was evaluated by mitochondrial targeting. Results: The optimal formula of DLD/ Hyp-Lip was as follows the ratio of total phospholipids to hyperoside was 12.501, the ratio of total phospholipids to cholesterol was 6.001, and the dosage ratio of DSPE-PEG to DLD was 35, the encapsulation efficiency was (95.57 ± 0.56) %, the drug loading was (8.55 ± 0.57) %. The prepared liposomes had good appearance, the particle size of the lip was (124.9 ± 3.4) nm, and the potential was (-6.2 ± 1.9) mV. It was stable in fetal bovine serum and accumulated in vitro release medium for 24 h. Mitochondrial targeting experiments showed that DLD/Hyp-Lip could promote the accumulation of drugs in the mitochondria. Conclusion: This method is simple and convenient, and can accurately and effectively optimize the preparation process of DLD/Hyp-Lip. The prepared DLD/Hyp-Lip has high encapsulation efficiency, small particle size, uniform distribution and good sustained-release effect, which lays the foundation for further in vivo research of DLD/Hyp-Lip. DLD/Hyp-Lip with hyperoside has good mitochondrial targeting of liver cancer cells and is a potentially efficient mitochondrial targeted drug delivery system for liver cancer cells.