No abstract

No abstract

We present a comprehensive investigation of the controlled dispersion polymerization of methyl methacrylate (MMA) in supercritical carbon dioxide (scCO 2 ) utilizing reversible addition fragmentation chain transfer (RAFT) polymerization to produce living microparticles. These microparticles show controlled molecular weight evolution, low polydispersities (PDI < 1.20), and well-defined spherical morphology (diameter ca. 1.40 µm). Four chain transfer agents are examined with modifications to both the stabilizing group (Z group) and leaving group (R group). We investigated their impact on molecular weight evolution and the morphology of the resulting polymer products in scCO 2 . The rate retardation effect intrinsic to many RAFT reactions which provides good kinetic control was shown to be much larger than that observed in analogous solution polymerizations performed in conventional organic media. This is believed to be due to the combination of the RAFT mechanism and the dispersion mechanism in scCO 2 .

A combination of thiol-yne chemistry and esterification reactions were successfully applied for the preparation of dendrimers with an array of terminal functionalities via the divergent growth strategy; maximizing the number of reactive chain ends whilst minimizing the number of reaction steps required in the process.

Hollow poly(6-O-acryloyl-alpha-D-galactopyranose) (PAGP) nanospheres were prepared in a facile manner using the RAFT (reversible addition fragmentation chain transfer) process. Initially, an amphiphilic block copolymer, poly(lactide)-block-poly(6-O-acryloyl-alpha-D-galactopyranose) (PLA-b-PAGP), was synthesized using a poly(lactide) (PLA) macroRAFT agent. It was attained in high yields and displayed low PDI values. The block copolymers self-assembled in aqueous solution to form micelles with pendent galactose moieties covering the surface. By using hexandiol diacrylate the micelles were cross-linked at the nexus of the copolymer, creating stable aggregates. Aminolysis with hexylamine allowed the removal of the PLA core without any detrimental effect on the glycopolymer units to produce hollow nanocages. Characterization of these hollow "sugar balls" with transmission electron microscopy (TEM) showed the cross-linked micelles with a central void due to the removal of the hydrophobic block. These micelles are advantageous in drug delivery applications, especially those involving the liver, thanks to the pendent galactose functionalities covering the surfaces of the nanocages.

Recently, controlled radical polymerization techniques have received considerable interest because of the ability to synthesize species exhibiting precise molecular architecture. 1 The (reversible addition fragmentation chain transfer) RAFT technique allows the formation of polymers with a very narrow molecular weight distribution from a wide range of monomers. 2,3 In addition, the resulting polymer is free from undesirable metal catalysts that are present following other controlled polymerization techniques (e.g., atom transfer radical polymerization). 4 Other authors have shown that RAFT-mediated polymerizations can occur in supercritical CO 2 , and product with low polydispersity (PDI), albeit low conversion, was generally observed. [5][6][7][8] Hydrophilic/CO 2 -philic stabilizers were synthesized by RAFT 9,10 and in one case used in the dispersion polymerization of poly-(hydroxyethyl methacrylate). 9 However, the RAFT-terminated stabilizer was not used to control the kinetics of the polymerization, and low PDIs were not observed. Our work takes a significant step further, yielding high conversion, high molecular weight polymer and living microparticles.Supercritical fluids have emerged as acceptable replacements for organic solvents. scCO 2 is nontoxic, nonflammable, and inert and has an easily accessible critical point (T c ) 31.0 °C, P c ) 7.38 MPa). 11 Since the first successful radical dispersion polymerization in scCO 2 by DeSimone and co-workers, 12 numerous authors have reported successful polymerizations of various vinyl monomers. [13][14][15][16][17] While careful control of the solvent density can lead to polymer particles with well-defined morphology, simultaneous control over the polymer molecular weight remains elusive.

This report presents the first simultaneous, metal-free synthesis of block copolymers through combination of enzymatic ring-opening polymerisation of epsilon-caprolactone with RAFT-mediated controlled radical polymerisation of styrene.

A drug-delivery system for albendazole (ABZ) based on β-cyclodextrin has been synthesized. Well-defined statistical copolymers, composed of N-isopropylacrylamide (NIPAAM) and trimethylsilylpropargyl acrylate (TMSPA), have been prepared by reversible additionÀfragmentation chain transfer (RAFT) polymerization. The reactivity ratios were determined to be r TMSPA = 1.12 and r NIPAAm = 0.49, in the absence of RAFT agent, and r TMSPA = 1.35 and r NIPAAm = 0.35, in the presence of RAFT agent using the average of different techniques. Block copolymers were prepared using a POEGMEA 40 macro-RAFT agent chain extended with NIPAAm and TMSPA in various feed ratios. After deprotection, the polymers were reacted with 6I-azido-6I-deoxy-β-cyclodextrin via Huisgen azideÀalkyne 1,3dipolar cycloaddition, resulting in thermo-responsive block copolymers with pendant β-cyclodextrin groups, which were then acetylated to modify the polarity and inclusion-complex formation of β-cyclodextrin with the drug albendazole (ABZ). Only block copolymers with small amounts of cyclodextrin were observed to have an LCST while the copolymers containing higher β-cyclodextrin fractions increased the LCST of PNIPAAm beyond measurable temperature ranges. Encapsulation of ABZ increased the LCST. The loading efficiency increased in the polymer β-cyclodextrin conjugate compared to native β-cyclodextrin with the highest loading observed in the block copolymer after all remaining cyclodextrin hydroxyl groups had been acetylated. While β-cyclodextrin is toxic, attachment of a polymer lowered the toxicity to nontoxic levels. The ABZ-loaded polymers were all observed to be highly toxic to OVCAR-3 ovarian cancer cell lines with the acetylated polymer showing the highest toxicity.