Photo-responsive Micelles Based On Non-linear Polymers For Controlled Drue Release

Polymeric micelles self-assembled from amphiphilic polymers have attracted more and more attention in the field of drug delivery due to their distinct advantages including improved solubility of hydrophobic anticancer drugs and prolonged circulation time. Additionally, controlled drug release can be achieved by molecular design to prepare stimuli-responsive micelles. In this study, amphiphilic non-linear polymers were synthesized by introducing hydrophobic photo-responsive groups into the structures of hydrophilic non-linear polymers. Photo-responsive micelles with excellent biocompatibility were then constructed by solution self-assembly. Model drug was at last encapsulated into the micelles to explore the possibility of the micelles as smart drug carriers for controlled drug release. The detailed two works are as follows:Biocompatible Micelles Based on Comb-Like PEG Derivates:Formation, Characterization and Photo-ResponsivenessA novel comb-like derivative CPEG-g-DNQ was prepared by incorporating light responsive2-diazo-1,2-naphthoquinone (DNQ) groups into the structure of comb-like poly(ethylene glycol)(CPEG). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that CPEG-g-DNQ self-assembled into spherical micelles with an average size of about135nm in water. The critical micelle concentration (CMC) of the micelles was determined as0.064mg mL-1by fluorescence spectroscopy using Nile Red as a fluorescence probe. MTT assay revealed that the micelles are biocompatible. Upon exposure to light, the micelles could be disrupted because of the conversion of hydrophobic DNQ to hydrophilic3-indenecarboylic acid. Additionally, hydrophobic coumarin102was successfully loaded into the micelles and photo-induced ON-OFF release was demonstrated by fluorescence spectroscopy. These photo-responsive micelles might have great potential for controlled release of hydrophobic drugs. Biocompatible and reversibly photo-responsive micelles constructed from spiropyran-modified hyperbranched polyphosphates for smart drug delivery Biocompatible and reversibly photo-responsive micelles were constructed from an amphiphilic spiropyran-containing hyperbranched polyphosphate (HPHEEP-SP) and applied for controlled release and re-encapsulation of drugs. HPHEEP-SP was designed and synthesized by modification of hydrophilic hyperbranched polyphosphate (HPHEEP-OH) with hydrophobic, light-responsive spiropyran (SP) molecules. DLS and TEM measurements revealed that the polymer can self-assemble into spherical micelles with an average diameter of186nm in aqueous solution. The critical micelle concentration (CMC) of the micelles was0.052mg ml-1determined by fluorescence spectroscopy using Nile Red as a fluorescence probe. Cell viability tests against two types of cells indicated that the micelles have excellent biocompatibility. By illuminating the micelles with365nm UV light, the diameter of the micelles decreased gradually to about100nm because of the transformation of hydrophobic spiropyran to hydrophilic merocyanine. Followed irradiating the micelles with620nm visible light, the diameter of the micelles was restored. Anticancer drug doxorubicin was successfully loaded into the micelles with loading content of8.98%and loading efficiency of49.33%. In vitro release experiments revealed that the drug-loaded micelles showed significant sustained release behavior. At last, model drug coumarin102was also encapsulated into the micelles. Then, controlled release under365nm UV light and re-encapsulation under620nm visible light were demonstrated by fluorescence spectroscopy. These photo-responsive and biocompatible polymeric micelles self-assembled from spiropyran-modified hyperbranched polyphosphates might have great potential as smart carriers in the field of drug delivery.