Preparation Of Zein And Hyaluronic Acid Composite Carrier For Drug Delivery

Zein has been widely used in food processing and biological delivery drug systems due to its excellent self-assembly,good resistance to gastric acid decomposition,unique dissolution behavior,excellent biocompatibility,reproducibility,and biodegradability.Different drug delivery methods have different requirements for nanodrug carriers.In this paper,aiming at overcoming the bottleneck of both injection and oral administration methods,Zein and Hyaluronic acid（Zein-HA）-based nanocarriers were elaborately designed with chemically modification,and its physicochemical properties and biological cell level characterization were investigated.The main research contents are as follows:（1）Amphiphilic Zein-HA-based nanoparticles were prepared using stirring dialysis method.An orthogonal array OA₁₆（4³）was employed to determine the optimal levels of multi-factors during the design of formulations.Zein-HA nanoparticles with narrow size distribution and homogeneous morphology were obtained.PEGylated Zein-HA（Zein-HA-PEG）nanodrugs showed HAase-triggered and p H-induced drug release and charge reversal ability in vitro conditions.Further biological level experiments showed that Zein-HA-PEG based nanodrugs enabled high CD44 specific cell uptake ability,strong cytotoxicity,and high tumor permeability,which are suitable for injection drug delivery pathways.（2）Zein-HA-based nanoparticles were prepared using ultrasound dialysis method.An orthogonal array OA₁₆（4⁴）was employed to determine the optimal levels of multi-factors during the design of formulations.Zein-HA@HCPT nanodrugs showed exhibit excellent biological stability,controlled release treatment capabilities,and unique anti-gastric acid decomposition properties in vitro conditions.The crystal structure of the encapsulated HCPT was amorphous,which was conducive to drug dissolution and bioavailability.Furthermore,in vitro simulated gastrointestinal release experiments demonstrated Zein-HA@HCPT excellent colon targeting properties Cytotoxicity results showed that the Zein-HA nanocarriers exhibited safe biocompatibility,while Zein-HA@HCPT nanodrugs have high cytotoxicity.（3）Using EDC/NHS to activate the chemical coupling of-COOH and L-arginine（L-ARG）in HA,Zein-HA-LARG@DOX with both gas therapy and chemotherapy functions was successfully prepared.Zein-HA-LARG@DOX showed excellent NO release ability in a simulated cell microenvironment in vitro.In the meanwhile,Zein-HA-LARG@DOX nanodrugs showed high L-ARG drug loading efficiency（9.8%）and DOX drug loading efficiency（10.3%）,and the in vitro release of NO and DOX experiments have further confirmed that Zein-HA-LARG@DOX have excellent acid and HAase sensitive drug release.Cytotoxicity experiments further demonstrated that NO can promote the sensitivity of cancer cells in response to DOX.In summary,aiming at solving the bottleneck problems of poor permeability and low penetration ability of nano drugs in intravenous injection,as well as the weak targeting ability in oral dosage forms,targeted nanodrugs based on zein and hyaluronic acid composite carriers with acid sensitive and enzyme sensitive characteristics have been designed,which provides new ideas for achieving target drug delivery.