Study On Adsorption Behavior Between PVDAT Functional Nanoparticles And Small Drug Molecules

Functionalization of the surface of polymer materials to achieve physical adsorption of target molecules has great application potential in many fields.Hydrogen bonding is an ideal physical adsorption force,but many adsorptions are carried out in the aqueous phase,and water molecules have strong hydrogen bonding formation ability,which often weakens or even destroys the hydrogen bonding between the adsorbent and the adsorbate.Therefore,there are technical challenges in how to achieve stable hydrogen bond adsorption in the aqueous phase,which has certain research significance.In this paper,by studying the adsorption of water-soluble small molecule drugs in the aqueous phase of 2-vinyl-4,6-diamino-1,3,5-triazine?VDAT?polymer?PVDAT?,discuss the importance of the synergy between hydrogen bonding and hydrophobic affinity in physical adsorption.In the study of PVDAT functional nanoparticle adsorption,this paper selected 5-FU,thymine,theobromine and xanthine,which can form triple H-bonding with PVDAT nanoparticles.Adsorption thermodynamics and saturation kinetics experiments were carried out at pH 7.4 and ionic strength of 200 mmol/L.The fitting equations inferred that the adsorption of small drug molecules to PVDAT was physical monolayer adsorption.The saturated adsorption amounts were 0.053 mmol/g?5-FU?,0.094 mmol/g?thymine?,0.0078 mmol/g?theobromine?,and 0.0065mmol/g?xanthine?.Even if triple H-bonding are formed at the same time,the steric hindrance effect of theobromine and xanthine is an important reason why the amount of adsorption is one order of magnitude less than that of 5-FU and thymine.Two methyl groups in theobromine may contribute to the H-bonding by repeling water molecules.The synergistic effect of hydrophobic affinity and hydrogen bonding results in even theobromine with a larger steric hindrance effect still having a larger saturation adsorption capacity than xanthine.The adsorption capacity of thymine is almost twice that of 5-FU.This may be due to the effect of 5-FU fluorine on hydrogen bonding.Fluorine in 5-FU has a low polarizability of electron pairs,and the ability of fluorine to accept hydrogen bonds is very weak,while fluorine only contributes very little to the electron transfer n??*.On the other hand,the electron-withdrawing effect of the 5-FU fluorine atom weakens its adjacent C=O as a hydrogen bond acceptor.In contrast,the electron-donating effect of-CH₃ in thymine may make the triple hydrogen bond with the DAT part stronger than 5-FU.These results also indicate that the adsorption between PVDAT nanoparticles and small drug molecules is a combination of multiple physical bonds.Research on the effect of adsorption conditions on the physical adsorption of PVDAT nanoparticles in water phase,by adjusting the pH or ionic strength of the buffer,and introducing hydrophilic PEG short chains on the surface of PVDAT nanoparticles,to change the surface of drug molecules or PVDAT nanoparticles,such as ionization state and hydrophilicity further explore the importance of the synergistic effect of hydrogen bonding and hydrophobic affinity.At pH 6 and 7.4,DAT and drug molecules are both in a non-ionized state,with strong hydrogen bonding and hydrophobic affinity synergy.DAT and each drug molecule can simultaneously form triple hydrogen bonds to achieve stable physical adsorption.When the pH value is lowered to 4.5,the hydrophilicity of the PVDAT nanoparticles on the surface of the DAT is increased due to protonation,which further weakens or destroys the synergistic effect of hydrogen bonding and hydrophobic affinity,which is not conducive to drug adsorption,so the saturation adsorption amount is reduced.As the pH value increases to greater than the pKa of the drug molecule,the drug molecule is deprotonated and becomes negatively charged,and then the electrostatic attraction between the surface of the positively charged PVDAT nanoparticles increases and the amount of adsorption increases.By comparing the adsorption of 5-FU and thymine by PVDAT@PVDAT and PEG@PVDAT nanoparticles,it was found that the adsorption of the two drugs on the surface of PVDAT by hydrophilic molecular brushes reduced the adsorption of the two drugs by7.6%and 6.4%,respectively.As the reverse process of adsorption,the drug desorption test was done under different conditions.After reaching the saturation state of adsorption of various small molecule drugs,maintain a temperature of 25°C and conduct desorption studies at pH 7.4 and 4.5;and maintain a constant pH 7.4 and desorption at different temperatures?25°C,50°C and 70°C?the study.In accordance with expectations for physical adsorption,increasing temperature leads to faster desorption.When the pH drops from 7.4 to 4.5,the hydrophilicity of DAT increases,which in turn accelerates the desorption of small molecule drugs.While lowering the pH value has a greater effect on desorption than increasing the temperature,it is further verified that the synergistic effect of hydrogen bonding and hydrophobic affinity plays an important role in the physical adsorption of the aqueous phase.