Study On Drug Productivity Of HA-PDM Oral Nano Drug Delivery System For Protein Drugs

Objective:Hyaluronic acid(HA)has good physical and chemical properties,but hyaluronic acid is very soluble in water and severely limits the application of hyaluronic acid.In this experiment,hyaluronic acid with different molecular weights was self-assembled with 2-(Dimethylamino)ethyl methacrylate(DM)to colloidal particles(HA-PDM)by electrostatic interaction.Insulin(INS)as a model drug,the release behavior of insulin in the gastrointestinal environment was investigated to provide a novel carrier for protein drugs,and the influence of HA molecular weight on the carrier HA-PDM was determined.Methods:The cationic hydrophobic monomer DM and the anionic electrolyte HA can form an assembly by electrostatic interaction,and initiate the polymerization of the cationic monomer to form an amphiphilic colloidal particle.The single-factor method was used to optimize the preparation process of the composite colloidal particles HA-PDM.Zeta potential and particle size analyzer,TEM,SEM and FT-IR were used to evaluate the carrier.The INS was loaded with the electrostatic adsorption method and the high-efficiency liquid was used.The drug loading and in vitro release were determined by phase chromatography and a cell model was established to investigate the drug transmembrane transport.Results:The optimal process for HA-PDM production with different molecular weight HA was:50 kDa HA,DM:300 μL,KPS:1.5 mL,rotation speed:1300 rpm·min-1,temperature:70℃;500 kDa HA in DM:500 μL,KPS:2.5 mL,rotation speed:1560 rpm.min-1,temperature:70℃;1200 kDa HA:DM:500 μL,KPS:2.5 mL,rotation speed:1560 rpm.min-1,temperature:60℃ The optimum pH of HA-DM mixed solution is 6.0 and the reaction time is 4 h.The particle size of HA-PDM is in the range of 200-300 nm,and the Zeta potential value is about-30 mV.The drug loadings for INS were 1.08%,0.77%,and 0.40%,respectively,and the amounts released within 2 hours of artificial gastric juice were 53%,48%,and 35%,respectively.The release of artificial intestinal fluid within 48 hours:70%,62%,33%.The hypoglycemic effect was found to reach the lowest value at around 10 h after intragastric administration.The initial blood glucose concentrations were 56.45%,53.83%,and 64.13%,respectively,and the hypoglycemic effect was sustained for 24 hours.Conclusion:The molecular weight of HA has a certain influence on the preparation process of HA-PDM.At the same time,it affects the drug loading and in vitro release.The larger the molecular weight,the lower the drug loading and the slower release.It was found that HA-PDM can protect INS,reduce the degradation of INS in the gastrointestinal tract,increase oral absorption,and reduce blood glucose.