Studies On The Responsive Hydrogels And Hydrogen Bond-induced Vesicles As Drug Delivery Carriers

The stimuli-responsive amphiphilic diblock copolymers can self-assemble into various microstructures,such as spherical micelles,rod-shaped micelles,disc,vesicles,and so on.Compared to the commonly obtained micellar structure,the vesicles are distinguished by the coexistence of both aqueous interiors and hydrophobic bilayer membranes that can simultaneously encapsulate both hydrophilic and water-immiscible drugs,which have been widely used for drug delivery application.The non-covalent interactions between the polymer chains,such as hydrophobic interaction,hydrogen bond,and π-π stacking,are of great importance for the morphologies and structures of the self-assemblies.In other words,the assembly morphology can be shift from micelles to vesicles by adjusting the non-covalent interaction between the polymers chains.Different from conventional polymeric assemblies,hydrogels are three-dimensional,cross-linked networks,which also have been widely used for drug delivery application because of their excellent biocompatibility,high drug loading efficiency,and programmable release profiles.In addition,the external stimuli such as light,temperature,and so on,can be used to trigger the reversible or irreversible changes of the chemical structures or physical properties of the responsive polymers.Thus,responsive hydrogels and polymersomes were prepared based on the responsive polymers and their potential applications as drug carriers and controlled release of the loaded drug were studied extensively.This dissertation includes the following parts:1.The thermo-and photo-responsive triblock copolymers,poly(N-isopropylacrylamide)-b-poly(4-acry-loylmorpholine)-b-poly(2-((((2-nitrobenzyl)ox-y)carbonyl)amino)ethyl methacr-ylate)(PNIPAM-b-PNAM-b-PNBOC)were successfully synthesized through sequential RAFT polymerization and the resulting triblock copolymers can form hydrogels through a stepwise manner.The as-assembled hydrogels comprising both hydrophobic domains and hydrophilic aqueous phase can be used as drug carrier and concomitantly encapsulate water-soluble gemcitabine(GCT)and water-insoluble doxorubicin(DOX)drugs.The following co-release of GCT and DOX could be dramatically tuned by the UV light irradiation and temperature change that can cause gel-to-sol transition.2.The photo-responsive diblock copolymers,poly(ethylene oxide)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate)(PEG-b-PNBOC),poly(ethylene oxide)-b-poly(1-(2-nitorphenyl)-3,11-dioxo-4,12-diazatetr-adecan-14-ylethacrylate)(PEG-b-PNBOCA),poly(ethylene oxide)-b-poly((2-nitrophenyl)-3,12,21-trioxo-2,13,20-tri--oxo-2,13,20-trioxa-4,11,22-triazatertracosan-24-yl-methacrylate)(PEG-b-PNBOCB),poly(ethylene oxide)-b-poly(2-((((4-(((perylen-3-ylmethoxy)carbo-nyl)amino)benzyl)oxy)carbonyl)amino)ethyl methacrylate)(PEG-b-PPCB)were successfully synthesized through sequential RAFT polymerization,which can self-assemble in aqueous solution to polymeric assemblies with different morphologies and structures.By changing the chemical structure of the monomers,as well as the non-covalent interactions between hydrophpbic blocks of the block copolymers,the self-assembly morphology can be transformed from micelles into vesicles.The as-assembled vesicles obtained from PEG45-b-PNBOCB24 comprising both aqueous interiors and hydrophobic bilayer membranes can simultaneously encapsulate water-soluble DOX·HCl and water-insoluble Nile Red.The following co-release of NR and DOX HC1 could be dramatically tuned by the UV light irradiation.