Based On The Response Of The Synthesis And Properties Of The Star Block Copolymer Structure Stimulation

Star block polymers as a kind of polymers with unique architecture have become a hot spot in polymer science since its’ clear structure, simple branched chain, narrow molecular weight distribution, good reactivity and versatility. In additions, it has a unique space configuration and lower viscosity, higher chain end functionality, easier processing, better mechanical performance, and faster degradation speed, so it can be used in (porous) membrane materials, degradable materials, drug carriers, DNA and RNA carriers, and other fields. And this kind of copolymers may readily self-assemble into nanoscale micelles with core-shell structure by embedded embedding, hydrogen bonds, electrostatic actions, hydrophobic actions, and van der Waals force in aqueous solution. These micelles have low critical micelle concentration, good stability, biocompatibility and solubilization of the hydrophobic drug in the process of blood circulation. Consequently, these micelles have been widely used as a kind of important short-term drug release carrier. In particular, poly(methacrylic acid)(PMAA)/poly(4-vi-nyl pyridine)(P4VP) and poly(N-isopropylacrylamide)(PNIPAAm) can respectively form pH-responsive and thermosensitive block copolymers. These self-assembly micelle drug carriers not only have a passive target function, but also can realize the active targeting with human physiological environmental changes at the same time. Based on the above reasons, the aim of this work is to synthetize pH-responsive poly(4-vinylpyridine)-block-poly(methacrylic acid)(P4VP-b-PMAA) four-armed star-shaped block copolymers and thermosensitive polylactide-block-poly(N-isopropylacryl-amide)(t-PLA-b-PNIPAAm) tri-armed star block copolymer, and to study its’micelliz-ation as well as drug release behavior. The related content is as follows:1. pH-sensitive P4VP-b-PMAA four-armed star block copolymers were synthesized by hydrolysis of P4VP-b-poly(tert-butyl methacrylate)(P4VP-b-PtBMA), while synthesis of the latter was accomplished via an atom transfer radical polymerization (ATRP) approach using t-BMA as monomer, CuCl as catalyst,1,1,4,7,10,10-hexamethyltriethyl-enetetramine (HMTETA) as ligand and four-armed star P4VP-Cl4as macroinitiator. The chemical structure and molecular weight of the as-prepared block copolymers were characterized by FT-IR,1H-NMR, and GPC determination. The solution behaviors were investigated by surface tension technique, UV-vis transmittance, TEM, DLS, and zeta potentials measurements. The experimental results indicated that the copolymers can spontaneously assemble into nanostructured spherical-shaped core-shell micelles, with a critical micelle concentration (CMC) less than200mg/L, hydrodynamic diameters below250nm, and higher stability (as indicated in zeta potentials determination), depending on the environmental pH values and feed ratios. The transmittance measurements revealed that the block copolymers produce evident phase transition in aqueous solution at pH from6.5to7.0.2. Thermosensitive t-PLA-b-PNIPAAm tri-armed star block copolymers were synthes-ized by ATRP, Specifically, star-shaped polylactides (t-PLA) with trimethylolpropane as a center molecule was prepared by ring-opening polymerization (ROP) of lactide using Sn(Oct)2as catalyst. Subsequently, the synthesis of star-shaped t-PLA-Cl was accomplished by esterification reaction of star t-PLA with2-chloropropionyl chloride. The star-shaped block copolymer PLA-b-PNIPAAm was prepared using star-shaped t-PLA-Cl as initiator, HMTETA as ligand and CuCl as catalyst. FT-IR,1H-NMR and GPC analyses confirmed that the t-PLA-b-PNIPAAm star block copolymers have well-defined structure and controlled molecular weights. The block copolymers could form core-shell micelle nanoparticles due to their hydrophilic-hydrophobic trait in aqueous media, with the CMC values from6.67to32.91mg L"1, and low critical solution temperature (LCST) from34to39℃, which depended on the system composition. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin-loaded copolymer micelles, which showed that the camptothecin-loaded copolymer micelles had lower cytotoxicity than free camptothecin on L929cell. The in vitro drug release was carried out with camptothecin as a model drug in aqueous solution and simulative physiological environment. The evaluation of drug release and release kinetics showed that the copolymer micelles exhibited thermo-triggered targeting drug release behavior, and the cumulative release rate varies with temperature. Thus they have potential application values in drug controlled release.