Preparation And Preliminary Cytology Investigation Of Ferulic Acid Decorated Hyaluronic Acid

Objective To prepare hyaluronic acid targeted drug with ferulic acidas antitumor drug and hyaluronic acid as targeting ligand. To investigate theinhibition of HA-FA on A549cells over-expressing HA receptor(CD44) andHepG2cells low-expressing HA receptor (CD44).Methods Serine methyl ester was used as a linker to synthesisHA-FA targeted drugs. UV spectra,1HNMR were used to identify itsstructure, UV spectrophotometry was used to determine the binding rates forFA. The binding rate for FA was used as evaluation indicator to evaluate thestability of HA-FA. Dialysis bag method case was applied to study thereleasing rate of HA-FA at different release medium (pH7.4and pH5.5PBS)in vitro; MTT assay was applied to examine the cytoxicity of HA, FA andHA-FA on A549cells and HepG2cells.Results FA was successfully coupled with HA confirmed by UV,1HNMR, binding rate for FA was16.58%(FA:HA=1:1,molar rate). Thecytotoxicity experiment showed that the proliferation inhibition rate onA549cells was HA<FA <HA-FA,as it was HA<FA≈HA-FA on HepG2 cells.Conclusions UV spectrophotometry to evaluate the binding rate forFA was easy and convenient. The stability test result showed that HA-FAstored in4℃can be more steady. The drug releasing studies in vitro showedthat HA-FA had a sustained-release efficacy. MTT assays indicated thatHA-FA had the best inhibition rate on A549cells than FA. All resultsdemonstrated that HA-FA can actively deliver FA to tumor cells whichover-expressing HA recepters with HA binding to it specifically andenhance the inhibition rate on tumor cells.