PNIPAAm Block Research Articles

Novel multi-responsive P2VP-block-PNIPAAm block copolymers via nitroxide-mediated radical polymerization

Linear soluble multi-responsive block copolymers are able to form so called schizophrenic micelles in aqueous solution. Here, such polymers are prepared via nitroxide-mediated radical polymerization (NMRP). In a first step nitroxide-terminated poly(2-vinylpyridine) (P2VP) was prepared with different molecular weights and narrow molecular weight distributions. The best reaction conditions, optimized by kinetic studies, were bulk polymerization at 110 °C. Using P2VP as a macroinitiator, the synthesis of new soluble linear block copolymers of P2VP and poly(N-isopropylacrylamide) (PNIPAAm) (P2VP-block-PNIPAAm) was possible. The nitroxide terminated polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy, size exclusion chromatography (SEC) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Thermal properties were investigated by the differential scanning calorimetry (DSC). Block copolymers showed pH- and temperature-responsive solubility in aqueous media. By increasing the P2VP content, the phase transition temperature shifted to lower temperatures (e.g. 26 °C for P2VP114-block-PNIPAAm180). Depending on the resulting block length, temperature and pH value of aqueous solution, the block copolymers form so called schizophrenic micelles. The hydrodynamic radius Rh of these micelles associated with pH values and temperature was analyzed by dynamic light scattering (DLS). Such kind of block copolymers has potential for many applications, such as controlled drug delivery systems.

Temperature-sensitive behaviour of poly(glycidol)-b-poly(N-isopropylacrylamide) block copolymers

Temperature-sensitive poly(glycidol)-b-poly(N-isopropylacrylamide) block copolymers (PGl55PNIPAAmy) were synthesised and their aqueous solutions investigated by different methods including differential scanning calorimetry (DSC), UV-VIS spectroscopy as well as dynamic and static light scattering. The cloud point temperature (T c) depended on the composition of the investigated block copolymers and increased with decreasing length of the PNIPAAm block in PGl55PNIPAAmy copolymers. In contrast, the enthalpy of phase separation of PNIPAAm segments measured by DSC decreased with decreasing length of the PNIPAAm block in the polymer. These findings can be correlated with the behaviour of homo-PNIPAAm with similar molecular weights indicating that the influence of PGl on the local environment and phase separation of PNIPAAm chains is similar to the influence observed for PNIPAAm chains bearing different low molecular weight end group. Using DLS measurement, it was shown that the aggregation process depended on the PGl/PNIPAAm block ratio. If the PGl/PNIPAAm ratio was low, stable core-shell aggregates were formed. In contrast, the tendency to formation of large unstable, loose aggregates was observed for copolymers with high PGl/PNIPAAm ratio.

"Smart" diblock copolymers as templates for magnetic-core gold-shell nanoparticle synthesis.

We report a new strategy for synthesizing temperature-responsive gamma-Fe(2)O(3)-core/Au-shell nanoparticles (Au-mNPs) from diblock copolymer micelles. The amphiphilic diblock copolymer chains were synthesized using reversible addition-fragmentation chain-transfer (RAFT) with a thermally responsive "smart" poly(N-isopropylacrylamide) (pNIPAAm) block and an amine-containing poly(N,N-dimethylaminoethylacrylamide) (DMAEAm) block that acted as a reducing agent during gold shell formation. The Au-mNPs reversibly aggregated upon heating the solution above the transition temperature of pNIPAAm, resulting in a red-shifted localized surface plasmon resonance.

Synthesis, Nanostructure, Functionality, and Application of Polyfluorene-block-poly(N-isopropylacrylamide)s

A series of amphiphilic rod−coil diblock copolymers with a polyfluorene (PF) as a hydrophobic and light-emitting rod and a poly(N-isopropylacrylamide) (PNIPAAm) as a hydrophilic coil were prepared. Their micellar nanostructures and fluorescence properties were stimulated using solvents, e.g., water and tetrahydrofuran (THF)/toluene (1:10 by volume), which were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), atomic force microscopy (AFM), and fluorescence spectroscopy. A typical block copolymer P2 (Mn = 14 400, Mw/Mn = 1.80, the PF weight fraction is 9.4%) in water exhibited micelles with the PNIPAAm block as the corona, whereas the polymer showed inverse micelles in mixed organic solvents of THF/toluene with PF as the corona. Such different nanostructures resulted in their different fluorescence properties. The fluorescence spectrum of P2 did not indicate aggregations of the PF chains in the THF/toluene mixture. Blue emission with a high quantum yield (0.80) was observed. In contrast, strong aggregations of the PF chains were observed in the aqueous solution, resulting in low quantum efficient (0.26) fluorescence. These results clearly demonstrated that the functionality of the P2 could be tuned through the solvent stimuli. The micelles of P2 were further used as nanocarriers to load a water-insoluble tetrakis(mesityl)porphyrin (H2(Me3)TPP) into its micellar aqueous solution. Efficient fluorescence resonance energy transfer (FRET) between the PF (donor) and H2(Me3)TPP (acceptor) (as high as 98% quenching of donor emission) was observed in their micellar solutions. Moreover, FRET contributes significantly to the efficiency of singlet oxygen generation from H2(Me3)TPP molecules (with an efficiency factor of 2 as compared to non-FRET micelles). This study provided a feasible way to enable the application of water-insoluble porphyrin in aqueous solution and enhance its singlet oxygen generation efficiency.

Preparation of an amphiphilic triblock copolymer with pH- and thermo-responsiveness and self-assembled micelles applied to drug release

A novel amphiphilic ABC triblock copolymer, poly( N-isopropylacrylamide)-b-poly(styrene-alternate-maleic anhydride)-b-polystyrene (PNIPAAm-b-PSMA-b-PSt), was designed and synthesized by reversible addition fragmentation chain transfer polymerization. The copolymer can disperse in aqueous media at room temperature to self-assemble into pH- and thermo-responsive core–shell–corona micelles, with the hydrophobic PSt block as core, the pH-sensitive PSMA block as shell, and the thermo-sensitive PNIPAAm block as corona. The aqueous copolymer solutions exhibited lower critical solution temperature (LCST) values around 33.5–35 °C under pH 2.1–9.2 conditions via optical transmittance measurements. The critical micelle concentration values of the self-assembled micelles were about 18.6 mg/L at pH 2.1 and 21.1 mg/L at pH 6.9, respectively, relying on fluorescent probe techniques. An interesting pH- and thermo-dependent size of the micelles was observed by dynamic light scattering techniques, which showed that the micelle diameters were about 100–120 nm at 40 °C and 120–160 nm at 25 °C, corresponding to pH 2.1–9.2, respectively. Transmission electron microscopy observations showed that the resulting micelles as uniform nanoparticles existed in regularly spherical shapes. The folic acid-loaded micelles showed a remarkable pH- and thermo-responsive drug release behavior. These results indicate that the copolymer micelles may serve as a promising “intelligent” drug delivery system.

Synthesis, characterization, and stimuli‐sensitive properties of triblock copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(N‐isopropylacrylamide)

AbstractWell‐defined triblock copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(N‐isopropyl‐acrylamide) (PEO‐b‐PDMAEMA‐b‐PNIPAAm) was synthesized via sequential reversible addition‐fragmentation chain transfer polymerization (RAFT) of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) and N‐isopropylacrylamide (NIPAAm) using α‐methoxy‐ω‐S‐1‐dodecyl‐S‐α‐(α,α′‐dimethyl‐α″‐acetate) poly(ethylene oxide) (mPEO‐DDAT) as macro‐RAFT agent, AIBN as initiator in dioxane at 80°C. The polymerization data indicated that the both RAFT processes were well controlled. The molecular weights of macro‐RAFT agents showed the influence on the RAFT polymerization process. The final PEO‐b‐PDMAEMA‐b‐PNIPAAm triblock copolymer can form uniform micelles in aqueous media above the lower critical solution temperature (LCST) due to containing temperature‐sensitive PNIPAAm block. The micelle size and Dh were dependent on the composition of triblock copolymer and the pH value of the solution. The PEO‐b‐PDMAEMA‐b‐PNIPAAm triblock copolymer showed dual temperature‐ and pH‐sensitive property in aqueous media. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Preparation and characterization of nanoparticles using poly(N-isopropylacrylamide)-poly(ε-caprolactone) and poly(ethylene glycol)-poly(ε-caprolactone) block copolymers with thermosensitive function

Thermosensitive nanoparticles were prepared via the self-assembly of two different poly(e-caprolactone)-based block copolymers of poly(N-isopropylacrylamide)-b-poly(e-caprolactone) (PNPCL) and poly(ethylene glycol)-b-poly(e-caprolactone) (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using1H-NMR, turbidimetry, differential scanning microcalorimetry (micro-DSC), dynamic light scattering (DLS), and fluorescence spectroscopy. The copolymer mixtures (mixed nanoparticles, M1-M5, with different PNPCL content) formed nano-sized self-aggregates in an aqueous environment via the intra- and/ or intermolecular association of hydrophobic PCL chains. The microscopic investigation of the mixed nanoparticles showed that the critical aggregation concentration (cac), the partition equilibrium constants (Kv) of pyrene, and the aggregation number of PCL chains per one hydrophobic microdomain varied in accordance with the compositions of the mixed nanoparticles. Furthermore, the PNPCL harboring mixed nanoparticles evidenced phase transition behavior, originated by coil to the globule transition of PNiPAAm block upon heating, thereby resulting in the turbidity change, endothermic heat exchange, and particle size reduction upon heating. The drug release tests showed that the formation of the thermosensitive hydrogel layer enhanced the sustained drug release patterns by functioning as an additional diffusion barrier.

Controlling the Aggregation of Conjugates of Streptavidin with Smart Block Copolymers Prepared via the RAFT Copolymerization Technique

Block copolymers containing stimuli-responsive segments provide important new opportunities for controlling the activity and aggregation properties of protein-polymer conjugates. We have prepared a RAFT block copolymer of a biotin-terminated poly(N-isopropylacrylamide) (PNIPAAm)-b-poly(acrylic acid) (PAA). The number-average molecular weight (M(n)) of the (PNIPAAm)-b-(PAA) copolymer was determined to be 17.4 kDa (M(w)/M(n) = 1.09). The PNIPAAm block had an M(n) of 9.5 kDa and the poly(acrylic acid) (PAA) block had an M(n) of 7.9 kDa. We conjugated this block copolymer to streptavidin (SA) via the terminal biotin on the PNIPAAm block. We found that the usual aggregation and phase separation of PNIPAAm-SA conjugates that follow the thermally induced collapse and dehydration of PNIPAAm (the lower critical solution temperature (LCST) of PNIPAAm is 32 degrees C in water) is prevented through the shielding action of the PAA block. In addition, we show that the cloud point and aggregation properties (as measured by loss in light transmission) of the [(PNIPAAm)-b-(PAA)]-SA conjugate also depended on pH. At pH 7.0 and at temperatures above the LCST, the block copolymer alone was found to form particles of ca. 60 nm in diameter, while the bioconjugate exhibited very little aggregation. At pH 5.5 and 20 degrees C, the copolymer alone was found to form large aggregates (ca. 218 nm), presumably driven by hydrogen bonding between the -COOH groups of PAA with other -COOH groups and also with the -CONH- groups of PNIPAAm. In comparison, the conjugate formed much smaller particles (ca. 27 nm) at these conditions. At pH 4.0, however, large particles were formed from the conjugate both above and below the LCST (ca. 700 and 540 nm, respectively). These results demonstrate that the aggregation properties of the block copolymer-SA conjugate are very different from those of the free block copolymer, and that the outer-oriented hydrophilic block of PAA shields the intermolecular aggregation of the block copolymer-SA bioconjugate at pH values where the -COOH groups of PAA are significantly ionized.

Shell-Cross-Linked Vesicles Synthesized from Block Copolymers of Poly(d,l-lactide) and Poly(N-isopropyl acrylamide) as Thermoresponsive Nanocontainers

A polylactide (D,L-PLA) macroRAFT agent was prepared by utilizing a hydroxyl-functional trithiocarbonate as a coinitiator for the ring-opening polymerization. The length of the resultant polymer was controlled by the concentration of the coinitiator leading to the formation of two PLA polymers with M(n) = 12500 g mol(-)(1) (PDI = 1.46) and M(n) = 20500 g mol(-)(1) (PDI = 1.38) each with omega-trithiocarbonate functionality. Chain extension of PLA via the RAFT (free radical) polymerization of N-isopropyl acrylamide (NIPAAm) resulted in the formation of amphiphilic block copolymers with the PNIPAAm block increasing in size with conversion. TEM measurements of the aggregates obtained by self-organization of the block copolymers in aqueous solutions indicated the formation of vesicles. The sizes of these aggregates were influenced by the ratio of both blocks and the molecular weight of each block. The lower critical solution temperature (LCST) of the block copolymer was largely unaffected by the size of each block. UV turbidity measurements indicated a higher LCST for the block copolymers than for the corresponding PNIPAAm homopolymers. Stabilization of the vesicles was attained by a cross-linking chain extension of the PNIPAAm block using hexamethylene diacrylate. As the trithiocarbonate group was located between the PLA and PNIPAAm blocks, the chain extension resulted in a cross-linked layer between the core and corona of the vesicles.

A synthetic hydrogel with thermoreversible gelation, III: an NMR study of the sol–gel transition

AbstractThe sol–gel transition mechanism of a thermoreversible hydrogel composed of a copolymer comprising poly(N‐isopropylacrylamide) and poly(ethylene glycol) (PNIPAAm–PEG) was studied by NMR. The 1H– and 13C–NMR spectra measured on a PNIPAAm–PEG solution in 99.9% D2O showed a remarkable line width broadening of the PNIPAAm block of more than that of the PEG block, during thermally induced hydrogel formation. This result suggested that the mobility of the PNIPAAm block is more restricted than that of the PEG block during gelation. A crosslinked polymer network formation was ascertained by a sudden reduction in the spin‐lattice relaxation time (T1) of the residual HDO proton during gelation. The temperature dependency of the T1 values for the PNIPAAm and PEG blocks revealed that the microscopic condition of the PNIPAAm block in water was drastically changed during gelation, while that of the PEG block was unchanged. The experimental results from NMR supported the following gelation mechanism; that an aggregation of PNIPAAm blocks in the separate copolymers caused by hydrophobic interaction forms crosslinking points to give an infinite three‐dimensional network structure. The hydrated PEG chains in the copolymers provide the network with a swelling property in water, and prevent the aggregation from causing a macroscopic phase separation.