氟功能化胆碱磷酸脂质体用于胰岛素的口服给药.

Subcutaneous insulin (INS) injection as the main therapy method for diabetes shows adverse effects such as inconvenient use and hypoglycemia. Fortunately, the oral route of administration of insulin possesses more application potential. As one of the most mature drug delivery systems, liposomes exist some disadvantages in the oral administration of proteins or peptides, such as poor stability, low drug load, and limited mucus penetration. Herein, according to the phosphocholine (PC) component of the cell membrane, choline phospholipid with trifluoroethyl modified zwitterionic head (DPFCP) is designed and synthesized for constructing liposomes delivery system loaded with insulin (INS@DPFCP) for oral administration. By comparison with phosphate choline liposomes (INS@DPPC) and unfunctionalized choline phosphate liposomes (INS@DPCP), the physicochemical properties, drug release stability, mucus permeability, biocompatibility, endocytosis, and transport ability of INS@DPFCP are studied. The test results indicate that the particle size of INS@DPFCP is 185 nm, and drug entrapment efficiency is (47. 1±3. 9)%. Compared with INS@DPPC (27. 2%) and INS@DPCP (24. 5%), the amount of mucus aggregation for INS@DPFCP is 17. 15%. Hemolysis and cytotoxicity experiments show that INS@DPFCP gets good biocompatibility. When the mass concentration is as high as 1. 2 mg/mL, the hemolysis rate is 6. 88%, and the cell viability is above 90%. In addition, the endocytosis assay results demonstrate that INS@DPFCP is proved to be higher cellular uptake efficiency of Caco-2 cells, and the drug delivery accumulation reaches 47. 5% in 4 h. INS@DPFCP is expected to play an important role in diabetes treatment, and shows potential application in the field of proteins or peptides oral administration [ABSTRACT FROM AUTHOR]