Preparation Of Cyclodextrin Supramolecular Drug-loaded Hydrogels And Their Release Properties In Vitro

In this thesis,the synthesis and properties of cyclodextrin-based supramolecular drug-loaded hydrogels were studied.The specific research contents and conclusions are as follows:.In the second chapter of this thesis,two prodrug molecules grafted by cyclodextrin covalent bond were synthesized,which were DOX-2N-β-CD and FA-2N-β-CD.The anticancer drug doxorubicin was loaded into a folate functionalized supramolecular hydrogel using host-guest interactions of DOX-2N-β-CD,FA-2N-β-CD,Pluronic F127,and α-CD.The structure of DOX-2N-β-CD and FA-2N-β-CD was successfully synthesized by NMR and IR analysis.The structure of folate-functionalized supramolecular hydrogel by XRD technique was confirmed.The analysis showed that the gel samples showed characteristic diffraction peaks at 2θ=19.8° and 22.3°,indicating that the hydrogel structure was a pseudorotaxane structure.The appearance and internal structure of the hydrogel were observed by SEM and TEM.The gel exhibits flocculated and disordered morphology and internal porous structure.The effects of α-CD and DOX-2N-β-CD on the rheological properties and mechanical strength of supramolecular hydrogels were studied by rheological analysis.As the content of α-CD and DOX-2N-β-CD in the system increases,the elastic modulus of the gel increases,and the shear viscosity also increases.By studying the swelling properties of the hydrogel,it is found that the water is condensed.The gel exhibits strong temperature sensitivity;the in vitro release test of the hydrogel drug shows that the release of the drug molecule by the hydrogel can last for more than 72 hours,and has good drug release properties.And as the p H of the external environment decreases,the cumulative release rate of the drug becomes large.In the third chapter of this thesis,the prodrug molecule Hep-2N-β-CD with cyclodextrin covalently grafted heparin was successfully prepared.The drug monomer doxorubicin was embedded in a heparin-functionalized supramolecular hydrogel using the interaction of Hep-2N-β-CD,Pluronic F127 and α-CD.The nuclear magnetic resonance spectrum analysis and infrared spectrum analysis confirmed that the building element Hep-2N-β-CD was successfully synthesized.The analysis showed that the gel samples showed characteristic diffraction peaks at 2θ=19.8° and 22.3°,indicating that the hydrogel structure is a pseudo-rotaxane structure.The appearance and internal structure of the hydrogel were observed by SEM and TEM.It was found that the hydrogel exhibited flocculent and disordered morphology and internal porous structure.The effect of α-CD on the rheological properties of hydrogels was studied by rheological characterization.It was found that with the increase of α-CD content in the system,the elastic modulus of the gel increased and the shear viscosity increased.The swelling properties of hydrogels were studied and it was found that supramolecular hydrogels exhibited strong temperature sensitivity.The in vitro release experiments of hydrogels showed that the release of drug molecules by hydrogels lasted for more than 60 hours.Good drug release properties.And as the ambient temperature increases,the cumulative release rate of the drug becomes larger.