Construction And Application Of Hydrogel Nano-drug Carriers With Stimulus Response

The hydrogel can be processed into various shapes and it is suitable for the treatment of irregularly shaped tissue defects.Since the hydrogel can be designed to have different stimulus responsiveness,it can have a controlled release and a sustained release effect on the drug according to the environment of various diseases.It has broad application prospects in disease treatment.In this thesis,the application of nano-medicine into stimulus-responsive hydrogel is used as a drug carrier for local administration to treat periodontitis.And its application is studied.Mainly conducted the following research:(1)The new hydrophobic drug GSK2606414 for the treatment of periodontitis was made into nanometer to obtain a nano drug(NanoGSK)with uniform particle size,high encapsulation efficiency and good stability.At the same time,the polypeptide chain with sulfhydryl groups was used as a crosslinking agent to prepare an enzyme-responsive hydrogel,and NanoGSK was successfully loaded into the hydrogel.The in vitro drug release results of the drug-loaded hydrogel show that the drug-loaded hydrogel has a good slowrelease effect compared with the release of the free drug.In an environment containing collagenase,the hydrogel degrades faster and the drug release of the hydrogel is more,which proves that the drug carrier has a good controlled release effect.Using periodontal ligament stem cells as the cell experiment material,the cell experiment results show that the drug can be taken up by the cells and will not affect the growth and proliferation of normal cells.The results of in vitro osteogenic capacity and in situ regeneration capacity of periodontal tissue show that the drug-loaded hydrogel can significantly improve the osteogenic differentiation capacity of inflammatory cells.(2)Combining high-gravity technology and polymer-induced liquid precursor technology,calcium carbonate nanoparticles(nCaCO3)were successfully prepared.At the same time,GSK2606414 and minocycline(MINO)were loaded.The particle size of nCaCO3 is below 100 nm,and the drug loading can reach 64.6%.A hydrogel precursor material with multiple responsiveness was prepared.And a glucose-triggered active oxygen/acid dual response organic/inorganic nanocomposite hydrogel was prepared at an appropriate hydrogel forming ratio.Then two therapeutic drugs were loaded successfully.The results of in vitro degradation and drug release experiments show that this drug-loaded hydrogel can effectively release reactive oxygen species and degrade the hydrogel material in the presence of glucose.At the same time,the acidic environment caused by the generated gluconic acid can further promote the degradation of calcium carbonate nanoparticles and the release of loaded drugs.The research results prove that the organic-inorganic nanocomposite hydrogel system can control the release of therapeutic drugs in the tissue microenvironment of diabetic periodontitis.And it is a periodontitis drug slow and controlled release carrier with good clinical application prospects.