| Nanoparticles have attracted enormous attention in controlled drug release because they could improve the solubility and stability of drugs. Polymeric micelles and mesoporous silica are the most studied materials for controlled drug release. Block copolymer can self-assemble into core-shell structure in aqueous solution. Hydrophobic drugs can be loaded into micellar core to lower their toxicity in human body. However, polymeric micelles are easily to be biodegraded and disaggregated in the blood. As far as silica is concerned, size-matching between drugs and mesopore is usally necessary for efficient loading and controlled release of drugs, which in fact restrict the application of mesoporous silica as drug carrier. Thus, it is desirable to prepare nanoparticles with novel structures and multi-functions for controlled drug release. Inspired by protein channels in biomembranes, polymeric micelles with tunable channels are constructed and used for controlled drug release, and polymer/silica hybrid hollow nanoparticles with tunable channels are prepared using complex micelles as a template.A novel and well-defined triblock copolymer, poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG45-b-P(HEMA-g-PLA10)11-b-PNIPAM430), containing a biodegradable PLA block and a thermo-sensitive PNIPAM block, was synthesized by a combination of ring opening polymerization (ROP) and reversible addition-fragmentation chain transfer polymerization (RAFT). In aqueous solution, the copolymer could self-assemble into core-shell micelle with the inner hydrophobic PLA block as the biodegradable core and outer bis-hydrophilic PEG/PNIPAM block as the mixed shell at room temperature. Increasing the temperature above the lower critical solution temperature (LCST) of PNIPAM, the micelle converted into a core-shell-corona (CSC) structure due to the collapsed of PNIPAM block. The soluble PEG chains could stretch out the PNIPAM shell forming hydrophilic PEG channels. Doxorubicin (Dox), an anticancer drug, was used as a model drug for controlled release experiments. The DOX-drug loaded micelle with PEG channels displayed well controlled release behaviors.Two well-defined diblock copolymers of PLA-b-PNIPAM and PEG-b-PLA were synthesized by a combination of ROP and RAFT, In aqueous solution, comicellization of these two diblock copolymers at room temperature resulted in complex micelles with a biodegradable hydrophobic PLA core and a mixed hydrophilic PEG/PNIPAM shell. Above the LCST of PNIPAM, complex micelles could be converted into a core-shell-corona structure composed of a PLA core, a collapsed PNIPAM shell, and a soluble PEG corona. The PEG chains acted as channels in the PNIPAM shell for the exchange of substance between the core and external environment, through which small molecule such as drug could pass and macromolecules such as enzyme could not. The release of a model small molecule drug, ibuprofen, loaded in the micellar core was investigated. The release rate depended on the composition of the mixed shell. Higher content of PNIPAM in the mixed shell led to slower release of ibuprofen. Compared with core-shell micelles, complex micelles with the core-shell-corona structure avoided burst release of ibuprofen and inhibited degradation of PLA by lipase, a macromolecular enzyme.It is an efficient method to synthesize the hybrid hollow nanoparticles with tunable channels using thermo-responsive complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) as a template. Two well-defined diblock copolymers, poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP), were first synthesized by atom transfer radical polymerization (ATRP). With increasing the temperature (45℃) of their mixed aqueous solution, the complex micelles formed with the PNIPAM block as the core and the mixed soluble PEG/P4VP blocks as the shell at pH 4.0. Shell cross-linking of the complex micelles was achieved using 1,2-bis(2-iodoethoxy)ethane (BIEE) as a bifunctional agent. Silica was selectively well deposited on the P4VP block of the complex micelles forming a core-shell-corona structure with PNIPAM as the core, P4VP/silica as the hybrid shell, and PEG as the corona. The soluble PEG chains penetrated the hybrid shell as the corona to avoid the hybrid nanoparticle further aggregates. The PEG channels through which H2O molecule could pass formed due to the phase separation between the silica shell and the PEG chains. Decreasing the temperature to 4℃, the PNIPAM block became swollen and further soluble, the PEG-b-PNIPAM block copolymer escaped from the nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica within the pH range of 2.0-7.0. Thus hollow nanoparticles formed. It should be noted that in situ channels were obtained simultaneously in the silica shell due to the escape of PEG chains. These channels, which connected the inner space and the outer milieu, were promising for substance exchange.A new type of multifunctional nanoparticles containing magnetic Fe3O4@SiO2 sphere and biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate acid) (PEG-b-PAsp) was prepared. Silica coated on the superparamaagnetic core was able to not only achieve a magnetic dispersivity, but also protect Fe3O4 against oxidation and acid corrosion. The PAsp block was grafted onto the surface of the Fe3O4@SiO2 nanoparticles by amido bonds, and the PEG block formed the outermost shell. The anticancer agent doxorubicin (DOX) was loaded into the hybrid nanoparticles via electrostatic interaction between DOX and PAsp. The release rate of DOX could be adjusted by manipulating the pH value. |
