Study On Preparation And Responsive Release Of Hollow Multishelled Composites

In recent years,Hollow Multishelled Structure（HoMS）has become one of the most promising multifunctional structures because of its unique structure and composition advantages.The inner cavity and shell can provide enough space and sites for the loading of substances,which can realize high drug loading.Importantly,the surface of the hollow carrier can be combined with specific functional materials through hydrogen bonds,covalent bonds or electrostatic interactions,so that the pore channels of the hollow carrier are decorated with gating switches,which is beneficial to the controlled release of drug molecules.Under certain conditions,the surface-modified gating switch can prevent the drug from leaking in advance.However,under endogenous or exogenous stimulation,the gating is turned on,and its structure and conformation change,leading to drug release.Moreover,the confinement effect of nanopores can accelerate the transmission of molecules,which is beneficial to respond to external stimulation.Because of its unique time-space sequence and cell-like behavior,the hollow multishelled structure has made great progress in the field of drug sustained release.Based on the above ideas,we construct the stimulus responsive intelligent drug carrier by adjusting the composition,structure and surface characteristics of the hollow multishelled carrier,so as to realize controlled drug release.The main research contents of this paper are as follows:（1）Using carbonaceous microspheres as templates,hollow multishelled titanium dioxide with different shell layers was prepared by sequential template method.Then,based on the sol-gel transition of poly（N-isopropylacrylamide）（PNIPAM）near the low critical dissolution temperature（LCST）,the TiO₂HoMS@PNIPAM drug carrier with thermal response switch was designed and constructed.And its LCST was regulated by adjusting the content of hydrophilic monomer acrylamide（AM）.（2）Based on hollow multishelled MnO,MnO HoMS@PEG with p H responsive switch was constructed by polyethylene glycol（PEG）modification.In this work,manganese acetate tetrahydrate was used as manganese source,and the single,double,triple and quadruple shell Mn₂O₃hollow multishelled structures with different shell numbers were prepared by adjusting the p H of precursor solution.Then MnO HoMS with good crystallinity and complete morphology was prepared by reduction in H₂atmosphere.By adjusting the molecular weight,concentration and stirring conditions of PEG,the uniform coating of the inner and outer shells of MnO HoMS was successfully achieved.（3）TiO₂HoMS@PNIPAM was used as drug carrier,and small molecule doxorubicin hydrochloride（DOX）and large molecule bovine serum albumin（BSA）were used as model molecules for loading,and the loading performance and release performance were studied.The results showed that TiO₂HoMS@PNIPAM realized the thermal response release of DOX and BSA.