Preparation Of Stimuli-responsive Amphiphilic Block Copolymers Micells And Their Use As Drug Carriers

During the past two decades, stimuli-responsive polymeric micellar systems that sense and respond totheir environmental stimuli have been the focus of considerable interest in terms of both fundamental andapplied perspectives. Stimuli-responsive amphiphilic block copolymer can also be referred to as theenvironmental sensitivity copolymer, which are sensitive to environmental stimuli such as temperature, pH,ionicstrength, magnetic field and ultraviolet light. In a recent study, a single stimulus response systemswere limited because of they in response to single stimulus, so design synthesis multiple stimuli-responsiveblock copolymers become scholars the research focus. Fluorescent amphiphilic block copolymers havinghigh selectivity and sensitivity, the drug carrier materials with fluorescence response and tracer functionhave potential application value in drug delivery system. In this paper, fluorescent emission of8-hydroxyquinoline was modified with unsaturated bond, reacted with methacryloyl chloride to prepared afluorescent functional monomer, design synthesis fluorescent stimulus response amphiphilic blockcopolymers with monomer. The work was complied as follows:1.Amphiphilic diblock copolymer, poly(8-methacryloyloxy-quinoline-co-isobutylacrylate)-b-poly(N--(morpholino)ethyl methacrylate)(P(MAQ-co-IBA)-b-PMEMA), was designed and synthesized byreversible addition fragmentation chain transfer(RAFT) polymerization. The polymer thus formed wascharacterized by FT-IR spectroscopy,1H NMR spectroscopy, GPC and elemental analyses. TEM and DLSanalysis showed that the micelles to be spherically shaped with mean hydrodynamic diameter around100nm; in addition, the micelle display the ability to response to external pH stimuli, as DLS measurementsindicated, the diameter of the micelles decreased with the pH values increasing at the room temperature. Then Folic acid (FA) was used as a model drug to incorporate into P(MAQ-co-IBA)-b-PMEMA micelles,fluorescence spectra indicated that both micelle and FA-loaded micelle have fluorescence. We found that bymanipulating the pH value of the release solution, it was possible to control the releasing rate of FA.2. Amphiphilic diblock copolymer, poly(8-methacryloyloxy-quinoline-co-isobutylacrylate)-b-poly(N--(morpholino)ethyl methacrylate-co-isopropyl acryl amide)[P(MAQ-co-IBA)-b-P(MEMA-co-NIPAM)]，was designed and synthesized by RAFT polymerization. The polymer thus formed was characterized byFT-IR spectroscopy,1H NMR spectroscopy, GPC and elemental analyses. TEM and DLS analysis showedthat the micelles to be spherically shaped with mean hydrodynamic diameter around80nm; The copolymerexhibited a LCST of around38C via optical transmittance measurements； in addition, the micelledisplay the ability to response to external pH stimuli, as DLS measurements indicated, the diameter of themicelles decreased with the pH values increasing at the room temperature. Then Folic acid (FA) was used asa model drug to incorporate into copolymer micelles, fluorescence spectra indicated that both micelle andFA-loaded micelle have fluorescence. We found that by manipulating the pH value and temperature of therelease solution, it was possible to control the releasing rate of FA.3.Amphiphilic diblock copolymer (poly(N-isopropylacrylamide)-b-poly(diacetone acrylamide)(PNIPAM-b-PDAAM)， was synthesized by RAFT polymerization. Its structure and composition wereconfirmed by FTIR spectroscopy,1H-NMR spectroscopy and GPC. TEM and DLS analysis showed thatthe micelles to be spherically shaped with mean hydrodynamic diameter around150nm; The model drugfolic acid (FA) was loaded into the micelles as drug carrier material and the in vitro drug release behaviorwas investigated at body temperature.