Basic Research On Design,Preparation And Application Of Biomass-based PH-sensitive Drug-loaded Hydrogel

In recent years,functional hydrogels that regulate drug release rate by environmental changes such as pH,temperature or ionic strength have received significant attention in controlling drug delivery.In particular,pH sensitive hydrogels that can deliver drugs to designated locations by the difference in pH value between different parts have proven useful for targeted drug delivery systems.In this paper,different pH-sensitive hydrogels were synthesized by three methods,and the response behavior of hydrogels at different pH values was explored.In the first research work,a pH-sensitive hydrogel CMC/?-CDP@IBU that can be used for drug delivery to the intestine is synthesized with ibuprofen,N,N-dimethyl-l-adamantamine,carboxymethylcellulose and ?-cyclodextrin polymers as main raw materials.1H NMR,FTIR,SEM showed that the hydrogel was successfully synthesized.The swelling of the hydrogel was tested in aqueous solutions of different pH values.It was found that the swelling rate of the hydrogel under acidic conditions is much smaller than that under neutral or weakly alkaline conditions,and the swelling conforms to the second-order kinetic equation.In vitro simulation of IBU release in the digestive tract showed that the hydrogel released almost no drug under acidic conditions,while slowly releasing the drug under alkaline conditions.Within 240-1350 min,the release of IBU conforms to the Korsmeyer-Peppas model and is a non-Fickian diffusion mechanism.Within 240-1350 min,the release of IBU is consistent with the Higuchi model.The MTT assay also showed that IBU/Gel-(?)CDP-CMC has low toxicity to BGC-823 cells and Caco-2 cells,and this system can be used as a potential safe drug delivery system for drug release in the digestive tract.In the second research work,a hydrogel shell formed by cross-linking natural biopolymer gelatin with EDC/NHS coated the IBU-loaded porous material Cu-MOF to form a pH-sensitive capsule Gelatin/Cu-MOF@IBU for delivery of the drug to the intestine.For drug delivery in the intestines.FTIR,BET,XRD and SEM showed that the hydrogel capsule has been successfully synthesized.The swelling data of the hydrogel indicates that the hydrogel has a higher swelling ratio under acidic conditions than it does under neutral or weakly alkaline conditions.The drug release test showed that Gelatin/Cu-MOF@IBU can better protect the drug in the gastric juice(pH<1.2),prolong the stability of the drug preparation,and control the release of the drug in the intestinal tract.The MTT assay showed that Gelatin/Cu-MOF@IBU has low toxicity to Caco-2 cells.Therefore,Gelatin/Cu-MOF@IBU can potentially be used as an oral drug delivery system.In the third research work,the pH-sensitive nanocomposite hydrogel GGNPs-BA was prepared by Schiff base reaction using oxidized dextran,gelatin,ethylenediamine-y-cyclodextrin encapsulating betulinic acid and titanium dioxide.FTIR,Zeta potential and laser particle size analyzer and TEM showed that GGNPs-BA has been successfully synthesized,and has obvious embedding structure under TEM and its particle size is about 70-180 nm.The prepared hydrogel was subjected to degradation test under weak acid and weak alkali conditions,and it was found that the hydrogel was degraded under weakly acidic condition and was not sensitive to weak alkaline condition.Cell uptake experiments indicate that the drug successfully enters the cytoplasm.In vitro and in vivo anti-tumor experiments showed that the GGNPs-BA has a better tumor suppressive effect than other previously reported betulinic acid preparations(eg,BA/GCD inclusion complexes).