| In recent decades,drug carrier materials have been continuously developed and widely applied in many medical branches,especially in the diagnosis and treatment of tumors.However,due to the complexity of drug delivery and clinical application in vivo,the current commonly used drug carrier systems have been unable to meet increasingly complex clinical needs,and it is urgent to develop new multifunctional drug carrier materials.The host-guest supramolecules are a kind of self-assembled aggregates based on non-covalent bonds.Compared with the systems based on covalent bond cross-linking,the host-guest supramolecules have many advantages such as simple preparation,reversible self-assemble ability and multiple stimulus response and so on.They have great potential application value in the construction of drug carrier materials.Based on the host-guest supramolecular structure,this thesis aims to construct a novel multifunctional drug carrier utilizing the host-guest interaction of cyclodextrin.The main content is divided into the following two parts:(1)An amphiphilic polyrotaxane molecule containing glucosamine side groups was synthesized and a nano drug-loaded micelle with tumor targeting function was constructed therefrom.The polyrotaxane is composed of multiple ?-cyclodextrin rings threaded on a polymer chain of poly(ethylene glycol)with hydrophobic end-caps of cholic acid.The hydroxyl groups on ?-cyclodextrin were chemically modified by succinic anhydride and the target ligand glucosamine was successfully grafted.It can form nanomicelles through hydrophobic selfassembly in water and can be loaded with antitumor drug doxorubicin(DOX).The selfassembly and drug release properties of polyrotaxane micelles were characterized by dynamic light scattering,transmission electron microscopy and ultraviolet-visible spectrophotometry.The experimental results showed that the drug-loaded micelles have a drug loading of about 13.6% and an average particle size of 148 nm.The cumulative drug release of drug-loaded micelles under pH = 5.5 was faster than under physiological conditions,with a certain release control performance.In vitro cell experiments showed that by introducing the glucosamine unit into the polyrotaxane molecule,the drug-loaded micelles exhibited selective recognition of cancer cell 4T1 and had a good active targeting performance.Meanwhile,the maximal half inhibitory concentration was determined to be ca.2.5 mg/L for the DOX-loaded micelles,close to the value of free DOX.The polyrotaxane drug carrier has excellent biocompatibility and is easy to modify,which provides new ideas and strategies for targeted drug delivery.(2)A cross-linked poly(vinyl alcohol)(PVA)supramolecular drug loaded hydrogel based on cyclodextrin/cholic acid host-guest crosslinking was prepared.The system can be used for in situ gel forming and continuous delivery of drugs.?-cyclodextrin and cholic acid were grafted onto the low molecular weight PVA segment,separately,and the hydrogel system was easily formed in situ by mixing the low viscosity aqueous solutions of the two PVA-based polymers.The solid content of the gel can be as low as 7.0 wt%.The mechanical properties of the hydrogels can be tuned by varying the molar fractions of cholic acid units on PVA.The dynamic inclusion complexation of the host-guest pair allows the hydrogel self-heal rapidly at room temperature and restore its original mechanical properties in less than 1 minute.These PVA based polymers exhibited high biocompatibility as shown by in vitro cell and hemolysis experiments.In addition,we chose FITC-dextran as a macromolecular drug model to explore the sustained release properties of hydrogels,which can release about 74% dextran molecules slowly within 24 hours of physiological fluids.This kind of low-molecular weight PVA-based supramolecular hydrogels can be more convenient to be used as a drug carrier in the biomedical field,surpassing conventional hydrogels prepared through freeze-thaw method. |
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