Biocompatible Intelligent Core-shell Nanoparticles With High Solid Content Via RAFT Aqueous Dispersion Polymerization

Nano-hydrogel is a kind of water swelling，cross-linked hydrophilic nano polymer material,because of its high water content, fast swelling, biocompatibility,it is extensively researched andapplied.Nano-hydrogels are mainly used in oral administration or injection of biologicalmacromolecules, such as peptides, proteins and nucleic acid drugs.Intelligent nano-hydrogels canrespond to small changes in the environment and occur reversible phase transition, so they canrelease drug in a certain amount in the fixed point, time.Thermosensitive nanogel is a very important kind of intelligent nanogel,and now PNIPAM(Poly(N-isopropylacrylamide))is most extensively studied, however PNIPAM as thermosensitivepolymer has some drawbacks, such as insensitive to molecular weight and concentration ofelectrolyte, heat-sensitive lag when cooling and the toxicity of the monomer. These all limitPNIPAM widely used as a heat-sensitive polymer.To solve these problems, study of PNIPAM analogues is very necessary. PEG(polyethyleneglycol) is biocompatible material and non-toxic, soluble in water, so you can use polyethyleneglycol copolymer to replace the traditional thermosensitive polymer PNIPAM.PMEA (poly(2-Methoxyethyl Acrylate))is non-toxic material with good biocompatibility,difficult to dissolve in water,but its monomer MEA(2-Methoxyethyl Acrylate) is wellwater-soluble.So we try to study the RAFT dispersion polymerization of MEA in aqueous phaseto prepare nanoparticles with good structure and properties.The main contents are:1. A hydrophilic macromolecular transfer agent PPEGMA is used in MEA RAFT(ReversibleAddition-Fragmentation Chain Transfer Polymerization) dispersion polymerization in aqueousphase, redox initiator KPS/NaAs initiate the reaction at low temperature, the final nanogel hasgood core-shell structure and stability. Water as solvent, avoid the use of organic solvents, thepreparation process is environmentally friendly, this method is simple and easy to implement inlarge-scale industrial production.The prepared Polymers by this method are with low dispersion, nanoparticles have goodcolloidal stability and high solid content.The application of redox initiator can initiate the reaction at low temperature, saving energy.The option of this kind of chain transfer agent, provesto be non-toxic,and the monomer is biologically compatible, so it can be used in nano-medicine.2. We try to copolymerize MEA monomer and PEGA, attempt to change their molarcomposition, to prepare thermosensitive polymers. Benzyl ethyl trithiocarbonate as transfer agentand AIBN as the initiator, MEA copolymerized with PEGA in DMF, by regulating the molarratio of the two monomers, the final series of copolymers have continuous change in the LCSTand low molecular weight distribution, In addition,they are stable in nature and structure.3. With SDS as surfactant and KPS as thermal initiator in water, MEA copolymerizes withPEGA by traditional free radical polymerization, the final prepared nanogels are well-structuredand stable with regular morphology, uniform size, and show good heat-sensitivity.4. We have chosen the hydrophilic chain transfer agent poly (N,N’-dimethylacrylamide)PDMA, use the RAFT polymerization, the monomer2-Methoxyethyl acrylate (MEA) andpoly(ethylene glycol) methyl ether acrylate (PEGA,Mn=480) copolymerized in aqueous solution,synthesized nanogels with controllable core-shell structure are monodispersed in water and havea high solids content (24.5%).RAFT polymerization process can be well controlled, preparedpolymer has a low dispersion degree, the final nanoparticles have good colloidal stability andlow polydispersion.Particle size of the nanogels can be better controlled between30-100nm, andthe nanogels are stable in structure and property, with continuous change of the heat-sensitive,showing a good linear relationship, they may have potential use in the nano-medicine, becauseof their linear thermal change.