Hydrogel As The Colon-targeting Oral Formulation For Controlled Drug Release

This thesis consists of two parts:(1)A double cross-linked chitosan/alginate hydrogels as the colon-targeting oral formulations for controlled drug release;(2)Study of 3D printing technology to prepare alginate sodium/gelatin hydrogel for controlled drug release.?.A double cross-linked chitosan/alginate hydrogels as the colon-targeting oral formulations for controlled drug releaseIn order to solve multidrug resistance in tumor treatment,this work will combine the advantages of chitosan and sodium alginate to prepare a double cross-linked chitosan/sodium alginate(CS/SALG)hydrogels as drug carrier to deliver doxorubicin(DOX)for anti-tumor.The purpose of drug release in the colon is achieved and solve the drug's disintegration in the stomach.The results showed that chitosan/sodium alginate has a high loading capacity of 80% to doxorubicin and pH-controlled doxorubicin release.Drug release experiments demonstrated that the chitosan/sodium alginate dual cross-linked hydrogel has a good colon targeting effect.The doxorubicin release profiles were determined by in vitro release assay,and it was found that doxorubicin was released slightly under the acid condition and rapidly under the condition of pH 7.4,showed a controlled drug release from chitosan/sodium alginate hydrogel under different physiological conditions.Moreover,chitosan/sodium alginate exhibited lower cytotoxicity in CCK-8 assays,and also showed a good biocompatibility in vitro,while doxorubicin-loaded chitosan/sodium alginate hydrogels displayed obvious inhibition to tumor cells.Therefore,a double cross-linked chitosan/sodium alginate will have broad prospects for colon targeting delivery of drug.?.Study of 3D printing technology to prepare alginate sodium/gelatin hydrogel for controlled drug releaseThe result shows that conventional hydrogel beads release drugs too slowly,so we studied use 3D-Bioplotters printing tablets medicinal tablet to improve the drug release performance of hydrogels.3D printing technology has considerable potential for specific patient dosage forms.The use of 3D bioprint technology can quickly,efficient,accurate manufacturing of models of different sizes and complex internal structures,and the functionalization of models by mixing with drugs,active factors,cells,etc to achieve organ customization and controlled drug release.In this study,we demonstrated that a novel design method using caplets with perforated channels to accelerate drug release from 3D printed tablets for the first time.A single cross-linked 3D printed hydrogel and conventional hydrogel beads were prepared using gelatin and sodium alginate as the main materials.After comparing we found,this 3D printed hydrogel has excellent pH response.The drug release behavior of 3D printing model was similar to the traditional preparation method but the release effect is better.In vitro cytotoxicity assay showed that the blank sodium alginate/gelatin(SALG/GEL)hydrogels displayed no toxic effect on 3T3 cells,while doxorubicin-loaded sodium alginate/gelatin hydrogels displayed obvious inhibition to tumor cells.Hydrogels has good biocompatibility to meet the requirement that be applied after 3D printing without any post processing.