Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomes

A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property.  FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology.  The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and ¹H NMR.  Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L.  FA-PDCT-L showed spherical or ellipsoid shape.  The mean particle sizes were in the range of 111.6 − 126.9 nm, zeta potentials were from −6.54 mV to −14.13 mV and the drug encapsulation efficiency achieved 97.8%.  The observed values agreed well with model predicted values.  The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL.  The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months.  After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively.  This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.