The Preparation And Characterization Of A Macromolecule Prodrug-the Doxorubicin-loaded Calcium Pectinate

Objective:A novel delivery nanosystem（Ca-PDC）based on a doxorubicin-loaded calcium pectinate conjugates macromolecular pro-drug were synthesized for efficient antineoplastic drug delivery.Besides,we further evaluated its sustained-release characteristics,toxicity,and biocompatibility.Methods:1.Synthesis of Ca-PDC:we can get a PDC macromolecular pro-drug（our laboratory has been prepared）,which has been fabricated.PDC was conjμgated to calcium ions via carboxylic and calcium ions.Ca-PDC was verified by methylene blue（MB）adsorption experiments.2.Preparation and characterization of Ca-PDC:Egg-box Ca-PDC nanosystems were prepared by self-assembling in situ.PDC was conjugated to divalent calcium via carboxylic and calcium ions single factor analysis was used to optimize the preparation conditions.SEM was used to observe morphology of nanosystems.The Ca-PDC nanosystems size and distribution were analyzed by Nano particle and Zeta potential analysis instrument.Furthermore,drμg loading efficiency was measured by UV.The drug release performances in different pH in vitro were studied under simulated conditions.3.The in vitro biocompatibility study of Ca-PDC:cell viability of Ca-PDC and DOX in endothelial cells was evaluated by CCK-8;2%of the red blood cells hemolysis activity was investigated in rabbits and bovine serum albumin（BSA）adsorption of Ca-PDC and DOX.4.The in vitro on anti-tumor proliferative effect and sustained release of Ca-PDC drug research:anti-tumor proliferative effect of Ca-PDC and DOX in HepG2 was determined by CCK-8;absorption of Ca-PDC and DOX in HepG2 was observed by flow cytometry.Results:Our laboratory has been prepared the chemical structure of the PDC.PDC macromolecular pro-drug was identified by preliminary study.And the structure of the egg-box nanoparticles of joining calcium ions was identified by methylene blue adsorption experiment.Then,Ca-PDC was formed under certain condition:PDC:Ca（OH）₂:NaHCO₃=10:1:3,pH5.0-5.5,50℃,100rpm.The average particle size of Ca-PDC was about 123.5 nm.The encapsulation efficiency and drug loading were56.96%±2.8%（n=3）and 22.07%±2.6%（n=3）respectively.In vitro drug release study showed that Ca-PDCdisplayed a prolonged slow release profile in different pH.Assays for anti-tumor proliferative effect and flow cytometry demonstrated shown a sustained release property as compared to free DOX.A cell viability study against endothelial cells further revealed that Ca-PDC possesses excellent cell compatibilities and low cytotoxicities incomparison with free DOX.Hemolysis activity demonstrated the Ca-PDC has a greater compatibility in comparison with free DOX.Conclusion:The Ca-PDC displayed a slow release and stable properties.Besides,the Ca-PDC possessed better biocompatibilities and lower cytotoxicities in comparison with free DOX.Otherwise,Ca-PDC could reduce toxic and side effects,improved bioavailability.All shown Ca-PDC was a great potential for use as a drug delivery system in cancer therapy.