Preparation Of Fluorescent Micelle-hydrogel Complex And Study Of Its Performance As A Carrie

Polymeric micelles are widely used as oil-soluble anticancer drug carriers due to their unique core/shell structure.However,micelles are thermodynamically self-assembled structures formed by the action of reversible stabilizing forces,which will inevitably be disintegrated by multiple destabilizing mechanisms under complex in vivo/vitro environments,leading to drug release before reaching the target tissue.Therefore,stability is a key issue limiting the application of traditional polymer micelles as carriers.Studies have found that cross-linking of micelle shells and embedding them in hydrogels with swelling but insoluble properties are common methods to improve the stability of polymer micelles.Based on this,an intelligent fluorescent micelle-hydrogel composite with fluorescence imaging function and p H/redox dual responsiveness was constructed and investigated in this paper.While improving the stability of micelles,hydrophobic drug delivery by hydrogels was achieved,and its fluorescence function is conducive to detecting micelle aggregation,disintegration and intracellular distribution.The details of the study are as follows:1.Hydrophobic modified polyethyleneimine(PEI-C₁₂)was prepared,and aggregation-induced emission monomer（TPE）was modified in its molecular structure by mercaptoacetic acid click imine reaction（MALI）.Amphiphilic polyethyleneimine micelles with AIE phenomenon(PEI-C₁₂ AIE)were then prepared by solvent evaporation method.The resulted micelle structures indicated significant AIE effect with average particle size of 122.1±2.4 nm,and the critical micelle concentration（CMC）was 0.0123 mg/m L.2.Dextran hydrogels were prepared by Schiff base reaction using cystamine dihydrochloride（CYS）as a cross-linking agent,and then used as a matrix for the encapsulation of PEI-C₁₂ AIE micelles to construct fluorescent micelle-hydrogel complexes with fluorescence properties and p H/redox sensitivity.The fluorescent micelle-hydrogel complexes with dense network structure,excellent elasticity was observed by SEM tests and rheological studies.In addition,degradation experiments showed that the AIE micelles could be released from the hydrogels with an intact structure.3.Doxorubicin（DOX）was used as a hydrophobic model drug to analyze the drug loading capacity,drug release behavior and mechanism of the resulted fluorescent micelle-hydrogel composite.The results showed that the hydrogel complex was beneficial to improve the stability of the micelles,while its environmental sensitivity led to an increase in the cumulative drug release.However,their release mechanism was complex and affected by multiple processes including diffusion,swelling and erosion.In addition,in vitro cell labeling experiments revealed that the micelle-hydrogel complex has good cytocompatibility,and the released AIE micelles can be phagocytosed by cells with good fluorescence imaging ability.Therefore,the fluorescent micelle-hydrogel complex developed in this study can be used for the environment-sensitive release of hydrophobic drugs and can achieve visualization of drug delivery.