In vitro and in vivo evaluation of a novel folate-based amphiphilic multifunctional stabilizer for targeting tumors with paclitaxel nanosuspensions

Abstract

In order to improve the targeted delivery of the drug, a novel folic acid-modified paclitaxel nanosuspensions (FA-PEG-PTX NCs) delivery system was designed in the present study, and its target delivery ability was verified in vitro and in vivo models. Paclitaxel nanosuspensions were prepared by antisolvent precipitation using folic acid-modified polyethylene glycol monostearate (FA-PEG-MA) and D - α-tocopherol polyethylene glycol succinate (TPGS) as functional stabilizers. The FA-PEG-PTX NCs had an average particle size of 195.33 ± 13.31 nm, a PDI of 0.182 ± 0.022 and a zeta potential of - 12.4 ± 0.62 mV. The drug loading (DL) and encapsulation efficiency (EE) of FA-PEG-PTX NCs were 48.45 ± 3.34 % and 96.90 ± 1.81 %. Particle morphology showed that FA-PEG-PTX NCs had a rod-shaped structure with a smooth surface. XRD and DSC indicated that PTX existed mainly in an amorphous structure in the nanocrystals. FTIR showed no chemical reaction between PTX and stabilizer but rather physical interactions. In vitro dissolution experiments showed that nanocrystals significantly improved the PTX dissolution rate. Cytotoxicity assay and apoptosis assay showed that FA-PEG-PTX NCs had a stronger inhibitory effect on the proliferation and apoptosis of folate receptor-positive cells, Bel-7402 cells, compared with PEG-PTX NCs. In vivo studies showed that FA-PEG-PTX NCs and PEG-PTX NCs had long-lasting and targeted effects. In conclusion, FA-PEG-MA seems to be a promising stabilizer with targeting properties.