The investigation on a conjugate of 5-fluorouracil-1-acetic acid and galactosylated poly (aspartamide): synthesis, stability and liver targeting

In order to obtain a hepatotropic-targeting conjugate of the anti-tumor drug, 5-fluorouracil-1-acetic acid (5-FUA) was coupled with poly (asparthydrazide-co-2-hydroxyethyl aspartamide) (PAHy-HEA), and the obtained poly (asparthydrazide-co-2-hydroxyethyl aspartamide)-5-FUA was reacted with lactobiono-1, 5-lactone to obtain a water-soluble hepatotropic conjugate of 5-FUA, galactosylated poly (asparthydrazide-co-2-hydroxyethyl aspartamide)-5-FUA (gal-PAHy-HEA-5-FUA). The successful preparation of the conjugate was confirmed by DSC, HPLC, FT-IR and UVspectra. The drug loading and galactose content of the gal-PAHy-HEA-5-FUA was 11.9% w/w and 18.9% w/w (24.2%mol/mol), respectively. The 5-FUA cumulative release from gal-PAHy-HEA-5-FUA in buffer solutions, plasma and liver homogenate was less than 3%, approximately 9 and 22% within 8 h, respectively. The conjugate was stable in buffer solutions and in plasma, and there was efficient drug release in targeted liver. In liver, the AUC and maximum concentration of 5-FUA from gal-PAHy-HEA-5-FUA was approximately 18-fold and 6-fold that from free 5-FUA, respectively, which showed that the 5-FUA conjugation to gal-PAHy-HEA is a promising strategy to enhance liver-targeting ability.