Preparation and properties of tumor-targeting lentinan-oleic acid polymer micelles based on folic acid for adriamycin delivery

Abstract

To develop a natural polysaccharide targeted nanomicelles drug delivery system loaded with the broad-spectrum anti-tumor drug adriamycin (ADM), FA-LNT-OA polymer was synthesized, the ADM/FA-LNT-OA polymer nanomicelles was prepared, and response surface approach was used to optimize the drug loading procedure of the ADM/FA-LNT-OA nanomicelles. Under the optimum conditions, the drug loading ratio was 14.36 ± 0.12% while the entrapment efficiency was 95.17 ± 0.13%. The drug-loaded micelles were spherical, with the size about 170 nm, and the size distribution was uniform. The CMC of ADM/FA-LNT-OA nanomicelles was 48 ± 0.46 μg/mL, their release was more sensitive to pH than that of ADM, and they had good stability. The FA-LNT-OA nanomicelles had good blood compatibility and cell compatibility. In vitro anti-tumor pharmacodynamic studies proved that the IC50 of ADM/FA-LNT-OA nanomicelles on Hela, ES-2 and A549 cells were 48.49 ± 0.25, 63.56 ± 0.68 and 105.93 ± 17.03 μg/mL respectively. Moreover, the plasma elimination half-life of ADM/FA-LNT-OA nanomicelles was 5.341 h, the Tmax was 0.083 h, the CL was 0.017 L/h/kg. Compared with the common ADM formulation, the ADM/FA-LNT-OA nanomicelles prolonged the clearance half-life of ADM, decreased the clearance rate, and extended the retention time of ADM in vivo. In conclusion, the above results laid the foundation for the increase of therapeutic effects and reduction of the clinical toxic and side effects of ADM.