A Photo-polymeric PEGDA-HA Hydrogel Drug Delivery System For Treatment Of Non-small Cell Lung Cancer

Local drug delivery system is a chemotherapy method.This method delivers anti-tumor drugs and acts on tumor cells directly.Compared with traditional chemotherapy methods,the main features of the local drug delivery method is drug concentration contained is higher,the relative drug dose is lower,the biological toxicity is lower,and the body adaptability is well.In recent years,more and more scholars have studied that hydrogel as a local drug delivery method delivers antineoplastic drugs for tumor chemotherapy.As we all know,hydrogel as a new type of bio-friendly material is increasingly studied for using in tissue engineering filed and drug delivery.Hydrogel is a water-based hydrophilic polymer,which can swell and maintain a lot of water,but can not dissolve with three-dimensional network structure.Hydrogel has sufficient stability and elastic function as a polymer.The hydrophilic group on the polymer chain is connected to water molecule with hydrogen bonds.Hydrogel has strong water lock function,which can hold more than 90%of the water.So it has both solid and fluid properties.And hydrogel have a good biological affinity and bioadhesive,its unique physical and chemical structure make it can be used as a local drug delivery system for tumor chemotherapy.The project designed a photopolymerized hydrogel PEGDA-HA.PEGDA-HA hydrogel consists of polyethylene glycol diacrylate(PEGDA),low molecular weight hyaluronic acid(HA),and photoinitiator 2-hydroxy-4'-(2-hydroxyethoxy)Phenylacetone(Irgacure 2959).The hydrogel is polymerized by UV light.In the preparation process,we explored the polyglycol diacrylate and the photoinitiator 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone in different mass ratios with different gelation time and chemical degradation rate.And we find an appropriate initiator to monomer mass ratio.In order to improve the biocompatibility of hydrogel,we introduced a polymer low molecular weight hyaluronic acid.In the course of the experiment,we investigated the swelling and degradation rate of hydrogel contained different low molecular weight hyaluronic acid.Thus,the ratio of PEGDA,HA,and Irgacure 2959 was determined.And PEGDA-HA photopolymerization hydrogel was prepared.We make PEGDA-HA hydrogel deliver paclitaxel nanoparticle PLGA-PTX and form PEGDA-HA/PLGA-PTX local hydrogel drug delivery system.During the experiment,PLGA-PTX nanoparticles were prepared by emulsifying solvent evaporation method.The nanoparticles were characterized by TEM and DLS.The results showed that the shell-core morphology of PLGA-PTX nanoparticles were very obvious.The drug loading was 7.4%,the encapsulation efficiency was 74.04%,and the size of nanoparticles were 170 2± 10.2nm,n = 3,PDI = 0.309 ± 0.089,n = 3,the particle size distribution is uniform.The zeta potential of nanoparticles were-4.64 ± 0.05mV,n = 3.By CCK8 experiment,we measured the IC50 of the PLGA-PTX nanoparticles is 10-5 527 mg/mL.By PLGA-PTX loading Dio fluorescein cell uptake experiment,we make sure that PLGA-PTX nanoparticles could be uptaked by NCI-H460 cells.From flow cytometry data we find that the NCI-H460 uptake rate of PLGA-PTX nanoparticle reached 96%.The drug release rate of PEGDA-HA/PLGA-PTX drug delivery system showed a rapid release rate of nearly 30%in the first 20 hours.And the drug release administration reached nearly 50%of the dose within 40 hours after administration.Then the drug release gradually slowed down.A dose of 65%drug was released within 100 hours after administration.Although the rate of release has slowed since then,there has been an upward trend.It is expected that the local hydrogel drug delivery system will maintain sustained drug release for 20 days at the site of tumor.We can see that the experimental group PEGDA-HA/PLGA-PTX has a tendency to decrease the tumor volume without toxic effects on mice.Which achieved the goal of killing tumor cells.The Observation of the experimental group PEGDA-HA/PLGA-PTX and the control group PBS H&E staining fluorescence picture,we can find that other organs didn't have tissue necrosis,while tumor tissue has tissue necrosis.Comparing TUNEL staining images of the experimental group PEGDA-HA/PLGA-PTX and the control group PBS,we found that there is no apoptosis was observed in other tissues except tumor tissue in the experimental group.The result of control group is normal.The whole experimental results showed that the PEGDA-HA/PLGA-PTX local hydrogel drug delivery system is a kind biocompatible local drug delivery system,which is directly applied by local direct administration.The PEGDA-HA/PLGA-PTX local hydrogel drug delivery system showed a good inhibition of tumor cell growth within 20 days after drug administration.