Study On Hollow Calcium Carbonate Nanospheres Modified With Hyaluronic Acid Derivatives For Hepatoma-targeting Delivery

Objectives A pH-responsive hyaluronic acid derivative modified active targeting drug-carrying hollow nanocarrier was prepared,based on the active tumor targeting capacity of hyaluronic acid,and calcium carbonate nanospheres with pH responsiveness to the tumor environment.Related performance measurements were performed.Methods Preparation of drug-loaded hollow calcium carbonate nanospheres:the drug-loaded hollow calcium carbonate nanospheres were prepared by the One-pot method,using starch as the template with CaCl₂ and Na₂CO₃,and doxorubicin hydrochloride as the model drug.Synthesis of conjugates:the use of hyaluronic acid and chitosan covalently combined to obtain hyaluronic acid-chitosan conjugates.Preparation of hyaluronic acid derivative modified hollow nanosphere carrier:the conjugate is modified by forming a coordination bond with Ca²⁺on the nanosphere to obtain a targeted drug delivery carrier with pH responsiveness.The particle size,Zeta potential,encapsulation rate,drug loading and in vitro release of the carrier were investigated.human liver cancer Hep G2 cells were used for cytotoxicity verification and in vitro anti-tumor activity evaluation by MTT experiment.H22tumor-bearing mice were used as a model,Verify the targeting effect of the vector and the tumor site in the body.Results 1 The hyaluronic acid-chitosan conjugate was successfully prepared,and the different coupling degrees of（3.67±0.16）%,（6.45±0.22）%,（13.32±0.24）%were obtained through determination,and the optimal conjugate feed ratio was obtained.2 The hollow drug-loaded nanospheres were successfully prepared.The transmission electron microscope image shows that the carrier is spherical and has a large hollow.The average particle size is（232.5±10.2）nm,the PDI is（0.358±0.060）,and the Zeta potential is（-25.1±0.4）m V.The modified hollow-targeted drug delivery carrier,the transmission electron microscope image shows that the carrier is spherical,with an average particle size of（376.8±12.4）nm,PDI of（0.295±0.080）,and Zeta potential of（-45.1±0.3）m V,the average particle size increased by144.3 nm.3 The measurement results show that the best encapsulation rate is（80.45±2.35）%,and the drug loading is（15.65±0.25）%.The in vitro release shows that the carrier has good pH responsiveness and has obvious slow-release characteristics.Toxicity experiments have proved that this carrier has low toxicity.4 Experiments in tumor-bearing mice proved that this vector has good hepatoma-targeting,hepatoma-targeting capabilities and antitumor activity.Conclusions A targeted delivery carrier of calcium carbonate hollow nanospheres modified by hyaluronic acid derivatives was successfully prepared.This carrier has good pH responsiveness,obvious slow-release characteristics,low toxicity,and this carrier has good hepatoma-targeted therapy ability.Figure15;Table24;Reference 105...