Study On PH-responsive Controlled Release Systems Based On Mesoporous Silica Nanoparticles And Polyurethane-polypeptide Nanogels

In this thesis,two kinds of drug controlled release systems were constructed based on mesoporous silica nanoparticles(MSNs)and nanogels respectively.The first one was inspired by the“gatekeeper”design concept.The long-term release system was prepared by surface modification of the MSNs in the way of post-synthesis.MCM-41 was used as the nano-reservoir of guest molecules and two kinds of biocompatible organic molecules,catechin and chlorogenic acid,were used as the gatekeeper to block the mesopores.The bond formed between the titanium isopropoxide and gatekeeper molecules can be cleaved by hydrolysis reaction gradually under neutral and alkaline conditions,so that the guests encapsulated in the mesopores can be released slowly.Chemical structure and composition of the pure MCM-41 and modified MCM-41 was characterized by FTIR,TGA,EDS,SEM,TEM,XRD and low temperature nitrogen adsorption analysis.The results showed that the pure MCM-41 nanoparticles were spherical or ellipsoidal,with ordered 2D-hexagonal mesopores,large specific surface area and pore volume.The particle diameter was between 100 nm and 150 nm and the pore size was about 2.8 nm.After modified by organic portions,the particle size increased,the mesostructure became less ordered,the pore size,specific surface area and pore volume decreased.The results proved that MCM-41 was modified with organic portions successfully.RhB as the guest molecule was loaded into this system and released in different pH to test the controlled release properties of this system.The results showed that catechin and chlorogenic acid can block the RhB molecules in mesopores effectively,which proved that catechin and chlorogenic acid can be used as gatekeepers.The MSNs based systems with different gatekeepers were of different release behaviors.When catechin was used as the gatekeeper,the system showed a distinctive release behavior of steadily releasing in pH 7.4 while no release under acidic conditions.Based on this release behavior,the system with catechin gatekeeper can be used for long-term release administration and also targeted drug delivery to the intestine,reducing the adverse effects of drugs on the stomach.When chlorogenic acid was used as the gatekeeper,the system showed similar long-term release behavior in pH 7.4 while,differently,it showed a certain release under acidic conditions.Based on this release behavior,the system with chlorogenic acid gatekeeper can be used for long-term release administration of non-targeted.The second one was a pH responsive controlled released system based on biocompatible waterborne polyurethane(WPU)and poly L-glutamic acid(PLGA).WPU and PLGA self-assembled into a core-shell nanogel by electrostatic interaction.The electrostatic interaction failed under acidic conditions and the secondary structure transition of PLGA occurred at the same time.These two effects made PLGA separated from WPU,so that guest molecules in WPU can be released.The NMR,FTIR,GPC and DLS characterizations proved the successfully synthesis of a series of WPU with various isocyanate index(NCO/OH)and ionic segment(MDEA)content,as well as a series of PLGA with various degree of polymerization(10,50,100).Besides,CD analysis verified the secondary structure transition of PLGA under acidic conditions.The effect of isocyanate index(NCO/OH)and ionic segment(MDEA)content on the particle size of WPU and the effect of COO~-/N~+ratio on WPU-PLGA self-assembled particle size were studied.Based on these study results,WPU-PLGA self-assembled nanogel applicable for drug released was successfully synthesized.Furthermore,RhB and Dox were used as the guest molecules for this system to test the loading capability.The test results showed that this WPU-PLGA system was suitable for loading hydrophobic molecules and anionic molecules especially,but not hydrophilic molecules.These two kinds of drug controlled release systems meet different requirements of drug administration in practical application,which have good prospect in the controlled drug delivery and biomedicine field.